What's new in oncology

Authors:: April F Eichler, MD, MPH; Diane MF Savarese, MD; Sadhna R Vora, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Aug 2018. | This topic last updated: Sep 28, 2018.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

BREAST CANCER

Aromatase inhibitor-induced joint pain and acupuncture (July 2018)

Aromatase inhibitors (AIs) are frequently used for the adjuvant management of hormone receptor-positive breast cancer, but they are associated with joint pain. In a randomized trial of over 200 women with joint pain due to AIs, acupuncture was compared with sham acupuncture and with waitlist controls [1]. Patients in the acupuncture group experienced close to a 1 point improvement in joint symptoms, on a scale of 1 to 10. Although the clinical significance of this small numerical improvement is unclear, some patients may wish to try acupuncture, particularly since there are no associated systemic side effects. (See "Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer", section on 'Side effects'.)

Updated guidelines on HER2 ISH interpretation in breast cancer (July 2018)

The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) has issued an update to guidelines on interpretation of results to define the HER2 status of breast cancers [2]. Specific differences relative to the 2013 guideline include interpretation of less common clinical scenarios when using the dual probe in situ hybridization (ISH) assay. For example, while previously a HER2/chromosome enumeration probe 17 (CEP17) ratio ≥2 was considered HER2-positive regardless of average HER2 copy number, the updated guidelines indicate need for further workup if the average HER2 copy number is <4 .0.="" cancers="" em="" similarly="" with=""> HER2

copy number ≥6 were previously considered HER2-positive regardless of HER2/CEP17 ratio, but further workup is now required for such tumors if the HER2/CEP17 ratio is <2 .0.="" a="" class="medical medical_review" ee="" href="https://www.uptodate.com/contents/her2-and-predicting-response-to-therapy-in-breast-cancer?sectionName=Differences+between+the+2013+and+2018+ASCO%2FCAP+guidelines&topicRef=8361&anchor=H1168367457&source=see_link#H1168367457" nbsp="" style="background-color: transparent; color: #00905a;">"HER2 and predicting response to therapy in breast cancer", section on 'Differences between the 2013 and 2018 ASCO/CAP guidelines'.)

Avoidance of adjuvant chemotherapy in women with HR-positive, node-negative breast cancer and intermediate Recurrence Score (RS) (July 2018)

The recurrence score (RS) identifies patients with node-negative, hormone receptor (HR)-positive early breast cancer whose prognosis is so favorable that the absolute benefit of chemotherapy is likely to be very low. Although previous data suggested no benefit from chemotherapy for those with low RS (<11 6700="" a="" adjuvant="" alone="" and="" assigned="" benefit.="" breast="" by="" cancer="" chemotherapy="" class="abstract_t" disease-free="" endocrine="" followed="" for="" hr-positive="" href="https://www.uptodate.com/contents/whats-new-in-oncology/abstract/3" if="" in="" intermediate="" it="" node-negative="" of="" postmenopausal="" randomized="" rates="" rs="" similar="" style="background-color: transparent; color: #00905a;" survival="" therapy="" those="" to="" trial="" unknown="" was="" were="" with="" women="" would="">3

]. However, the subset of women ≤50 years with RS>16 experienced lower rates of distant recurrence if they received chemotherapy. For most women with node-negative, HR-positive early breast cancer and intermediate RS, we suggest not administering chemotherapy, although chemotherapy is appropriate in women ≤50 years with high-intermediate RS. (See "Prognostic and predictive factors in early, nonmetastatic breast cancer", section on 'Validation in node-negative, HR-positive disease'.)

Duration of adjuvant trastuzumab in early HER2-positive breast cancer (July 2018)

The standard duration of adjuvant trastuzumab treatment for early HER2-positive breast cancer is one year. In the PERSEPHONE trial, among 4100 patients with HER2-positive early breast cancer, those randomly assigned to six months of adjuvant trastuzumab experienced noninferior four-year disease-free survival (DFS) rates relative to those receiving one year, with fewer cardiac events [4]. However, in the subset receiving concurrent chemotherapy and trastuzumab, which best mirrors contemporary practice, DFS was better in the 12-month group. Given these findings and previous trials demonstrating benefit for 12 versus 6 months of therapy, we continue to suggest that trastuzumab be administered for 12 months. However, for women who cannot tolerate 12 months of therapy, data from the PERSEPHONE trial are reassuring that the greatest amount of benefit is likely achieved within the first six months of treatment. (See "Adjuvant systemic therapy for HER2-positive breast cancer", section on 'Treatment duration'.)

Ovarian suppression with either tamoxifen or an aromatase inhibitor in premenopausal women with early breast cancer (July 2018)

Two trials have examined the efficacy of ovarian suppression (OS) added to either adjuvant tamoxifen or the aromatase inhibitor exemestane in premenopausal women with early breast cancer [5]. In the SOFT trial, compared with tamoxifen alone, OS plus tamoxifen improved eight-year disease-free survival rate (83 versus 79 percent), as did OS plus exemestane (86 percent) [5]. Women receiving OS experienced more musculoskeletal side effects, and for those receiving exemestane, higher rates of osteoporosis. Distant recurrence rates at eight years were lower for exemestane plus OS compared with tamoxifen plus OS in both trials. Given the greater toxicity associated with the addition of OS to other endocrine therapy, we suggest it for women with cancers at higher risk for relapse. For women with lower risk cancers, we suggest tamoxifen as single-agent therapy, although such women who prioritize minimizing breast cancer risks over side effects of treatment may also be appropriate candidates for OS with other endocrine therapy. (See "Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer", section on 'Average-risk premenopausal patients'.)

Mixed data regarding denosumab as adjuvant breast cancer treatment (July 2018)

Data are evolving regarding the use of the anti-RANK-ligand denosumab as an adjuvant breast cancer treatment. In preliminary results of one randomized trial of 3400 postmenopausal women receiving adjuvant aromatase inhibitors (AI), denosumab improved disease-free survival (DFS) [6]. However, in a separate trial of 4500 patients with early breast cancer, over half of whom were on adjuvant AI treatment, denosumab did not improve DFS in the overall population or in subgroups categorized by either tumor receptor or patient menopause status [7]. We continue to use denosumab for bone health indications only, rather than breast cancer outcomes, pending further data. (See "Overview of the use of osteoclast inhibitors in early breast cancer", section on 'Efficacy'.)

Addition of carboplatin to neoadjuvant chemotherapy for triple negative breast cancer (May 2018)

In general, patients with triple-negative breast cancer (TNBC) receive anthracycline- and taxane-based regimens as adjuvant or neoadjuvant chemotherapy (NACT). In the BrighTNess trial, over 600 patients with stage II to III triple TNBC were randomly assigned to standard NACT, the same NACT plus carboplatin, or the same NACT plus both carboplatin and the poly ADP-ribose polymerase (PARP) inhibitor veliparib [8]. The addition of carboplatin increased the pathologic complete response (pCR) rate from 31 to 58 percent, while incorporation of veliparib did not further increase the pCR rate. However, addition of carboplatin to NACT increases hematologic toxicity, and its effect on survival is uncertain. Some UpToDate experts favor adding carboplatin to NACT for patients with TNBC with tumors >3 cm, clinically positive nodes, or stage III disease, while others do not incorporate it, in general. If carboplatin is being considered, treatment decisions must be individualized and involve discussing the potential risks and benefits with patients. (See "General principles of neoadjuvant therapy for breast cancer", section on 'Triple-negative disease'.)

Chemotherapy after resection of locoregional breast cancer recurrence (May 2018)

For women who have undergone resection of an isolated, locoregional recurrence (ILRR) of breast cancer, the use of adjuvant chemotherapy has been controversial. In the final analysis of a trial of 162 patients with ILRR, adjuvant chemotherapy improved 10-year disease-free survival (DFS) compared with no chemotherapy in patients with estrogen receptor (ER)-negative, but not ER-positive, ILRR [9]. However, interpretation of the study is limited by the small patient number and variation in the treatments administered prior to locoregional recurrence [10]. As such, we generally offer adjuvant chemotherapy to women with ER-negative ILRR and adopt an individualized approach for those with ER-positive ILRR, taking into account the patient's prior therapy and likelihood of response to endocrine therapy alone. (See "Systemic treatment for metastatic breast cancer: General principles", section on 'Chemotherapy'.)

Family history and breast cancer risk among older women (April 2018)

Data suggest that family history is an important risk factor for breast cancer, although the magnitude of the risk for older women is controversial. In a prospective cohort study of over 400,000 women, a first-degree family history of breast cancer was associated with an increased risk of breast cancer for women ages 65 to 74 years that was similar to those 75 years and older [11]. In counseling women, we advise that a family history of breast cancer affects a woman’s risk of breast cancer, regardless of her age. (See "Factors that modify breast cancer risk in women", section on 'Family history of breast cancer'.)

CANCER SCREENING AND PREVENTION

Hydrochlorothiazide and risk of cutaneous squamous cell carcinoma (July 2018)

Previous studies found modest increases in risk for cutaneous squamous cell carcinoma (SCC) among patients using photosensitizing medications, and in particular, thiazide diuretics. A Danish case-control study including over 8000 patients with SCC and 172,000 controls found that, compared with nonusers, high users of hydrochlorothiazide had a two- to seven-fold increased risk of cutaneous SCC, with a clear dose-response effect [12]. Although additional studies controlling for known risk factors for SCC (eg, sun exposure, phototype, smoking) are still needed, education on sun avoidance and sun protection may be appropriate for patients taking thiazide diuretics. (See "Epidemiology and risk factors for cutaneous squamous cell carcinoma", section on 'Other photosensitizing drugs'.)

USPSTF prostate cancer screening guidelines updated (June 2018)

Whether to screen for prostate cancer is a subject of much research and discussion. The US Preventive Services Task Force (USPSTF) updated its recommendations, saying to individualize decision-making about prostate cancer screening for men ages 55 to 69, including informing each man about the potential benefits and harms of screening and eliciting his values and preferences for screening [13]. The USPSTF continues to recommend against screening men 70 years and older, and concluded that evidence was insufficient to make a specific recommendation regarding screening discussions for higher-risk groups: African-American men and those with a family history of prostate cancer. The USPSTF concluded that new evidence shows screening offers a small potential benefit for reducing prostate cancer mortality and metastatic disease, although many men will experience harms, including false-positive results, overdiagnosis, overtreatment, and treatment complications. (See "Screening for prostate cancer", section on 'Recommendations of others'.)

Advanced colorectal adenomas and cancer risk (June 2018)

Colorectal adenoma characteristics are an important determinant of the risk for colorectal cancer (CRC). A prospective cohort study included approximately 16,000 participants of a randomized trial who underwent colonoscopy for abnormal flexible sigmoidoscopy findings [14]. At a median follow-up of approximately 13 years, individuals with advanced adenomas (≥10 mm or with villous components or high-grade dysplasia) on that baseline colonoscopy had a higher risk of CRC and CRC death compared with those without adenomas (relative risks 2.7 and 2.6, respectively). Although there was no significant difference in CRC risk between individuals with non-advanced adenomas and those without adenomas, the study may have been underpowered. This study lends further support to existing recommendations that patients with advanced colorectal adenomas have close follow-up for CRC surveillance. (See "Overview of colon polyps", section on 'Risk assessment for subsequent colorectal cancer'.)

Updated ACS guidelines on colorectal cancer screening (May 2018)

The American Cancer Society (ACS) has updated its colorectal cancer (CRC) screening guidelines [15]. On the basis of an apparent increase in the incidence of CRC in younger adults, the ACS guidelines now make a “qualified” recommendation to begin screening persons at average risk for CRC at age 45 years, with a strong recommendation to screen at age 50 years and above. The guidelines also now offer six testing options to select among: colonoscopy every 10 years, computed tomographic colonography (CTC) every five years, sigmoidoscopy every five years, take-home high-sensitivity guaiac-based fecal occult blood testing yearly, take-home fecal immunochemical testing (FIT) yearly, and multitargeted stool-DNA test every three years, noting that any positive result on a noncolonoscopy test should be followed up with timely colonoscopy. In including more tests, rather than prioritizing tests that could detect both polyps and cancer, the ACS notes that screening with a test acceptable to the patient is preferable to the patient declining screening. For average-risk patients, and in keeping with most guidelines, we continue to initiate screening starting at age 50 years. We prefer colonoscopy when possible, and FIT or CTC if the patient cannot or will not have colonoscopy. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Other guidelines'.)

Guidelines for colorectal cancer screening in adults with cystic fibrosis (May 2018)

Individuals with cystic fibrosis have an increased risk for colorectal cancer and other digestive tract cancers. The Cystic Fibrosis Foundation (CFF) has developed new guidelines for screening for colorectal cancer in this population [16]. The guideline recommends screening colonoscopy beginning at age 40 years, or at 30 years for those who have had an organ transplant, and describes an intensive bowel preparation protocol that should be used for cystic fibrosis patients. (See "Cystic fibrosis: Overview of gastrointestinal disease", section on 'Gastrointestinal cancer'.)

Updated USPSTF guidelines on ovarian cancer screening (April 2018)

Despite the incidence of ovarian cancer, routine screening for ovarian cancer has not generally shown a mortality benefit for asymptomatic women not at high risk. The US Preventive Services Task Force (USPSTF) 2018 statement continues to recommend against screening for ovarian cancer for asymptomatic women who are not known to have a high-risk hereditary cancer syndrome [17]. The USPSTF notes that a woman with a family history of ovarian or breast cancer or symptoms should talk with her clinician. These recommendations are consistent with our approach. (See "Screening for ovarian cancer", section on 'Recommendations of expert groups'.)

GASTROINTESTINAL CANCER

Bevacizumab for protection of oxaliplatin-induced thrombocytopenia in metastatic colorectal cancer (September 2018)

Patients with metastatic colorectal cancer (mCRC) who are treated with oxaliplatin may develop dose-dependent hepatic sinusoidal injury (HSI) with consequent splenomegaly and thrombocytopenia. For patients with potentially resectable liver metastases, this increases the bleeding risk and postoperative morbidity. A cohort study suggested that the addition of bevacizumab may protect against HSI. In a randomized trial of 200 patients with unresectable mCRC treated with fluoropyrimidine and oxaliplatin, the addition of bevacizumab, compared with placebo, reduced the incidence of splenomegaly and thrombocytopenia [18]. However, the clinical impact of a reduction in thrombocytopenia on efficacy outcomes in patients with unresectable mCRC remains to be determined. (See "Management of potentially resectable colorectal cancer liver metastases", section on 'Issues related to bevacizumab'and "Systemic chemotherapy for metastatic colorectal cancer: Completed clinical trials", section on 'Hepatic sinusoidal injury'.)

Maintenance therapy options in metastatic colorectal cancer (August 2018)

Oxaliplatin-based regimens such as FOLFOX (oxaliplatin plus leucovorin and short-term infusional fluouracil [FU]) are frequently used for first-line chemotherapy in metastatic colorectal cancer (mCRC). Dose-limiting cumulative sensory neuropathy has prompted efforts to minimize oxaliplatin exposure by discontinuing oxaliplatin after three to six months, delivering maintenance oxaliplatin-free chemotherapy, and reintroducing oxaliplatin at the time of disease progression. Two trials have addressed maintenance therapy for patients treated initially with FOLFOX plus an inhibitor of the epidermal growth factor receptor (EGFR). In one trial, maintenance cetuximab alone was noninferior compared with continued FOLFOX plus cetuximab [19]. A preliminary report of another trial suggested that, following four months of FOLFOX plus panitumumab, treatment with panitumumab alone was inferior to panitumumab plus leucovorin-modulated FU [20]. In our view, maintenance cetuximab alone is an acceptable option for patients initially treated with cetuximab plus FOLFOX, but panitumumab plus leucovorin and FU is preferred over panitumumab alone for maintenance therapy in patients initially treated with panitumumab. (See "Systemic chemotherapy for metastatic colorectal cancer: General principles", section on 'Maintenance EGFR inhibitor'.)

Hemostatic nanopowder approved for use in gastrointestinal bleeding (July 2018)

Hemostatic nanopowder can be used to treat bleeding in the gastrointestinal tract due to lesions such as ulcers and tumors. It is sprayed onto a bleeding site under endoscopic guidance and forms a stable mechanical barrier at the site of bleeding. In prior reports, success rates for achieving initial hemostasis in patients with nonvariceal upper gastrointestinal bleeding are 75 to 100 percent, with rebleeding rates of 10 to 49 percent. In May 2018, Hemospray, a hemostatic nanopowder, was approved as a device by the US Food and Drug Administration (FDA) [21]. The data submitted to the FDA showed hemostasis on index endoscopy in 97.8 percent of 750 patients, with an overall rebleeding rate of 10.2 percent [22]. In patients with bleeding peptic ulcers, hemostatic sprays may be particularly helpful when a temporizing measure is needed to stabilize a patient pending definitive therapy or when traditional endoscopic techniques fail to control massive bleeding. (See "Overview of the treatment of bleeding peptic ulcers", section on 'Hemostatic nanopowder'.)

Adjuvant FOLFIRINOX after primary resection for pancreatic cancer (July 2018)

Multiagent chemotherapy regimens, such as FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, and short-term infusional fluorouracil) are more effective than gemcitabine alone in metastatic pancreatic cancer. The superior efficacy of FOLFIRINOX in the adjuvant setting was shown in the PRODIGE-24 trial, in which patients with resected pancreatic ductal adenocarcinoma were randomly assigned to six months of gemcitabine monotherapy or modified FOLFIRINOX (table 1) [23]. FOLFIRINOX improved disease-free and overall survival but was also more toxic, with higher rates of severe diarrhea, vomiting, sensory neuropathy, and fatigue. (See "Treatment for potentially resectable exocrine pancreatic cancer", section on 'Modified FOLFIRINOX'.)

Cabozantinib after sorafenib treatment for advanced hepatocellular cancer (July 2018)

Cabozantinib is a potent inhibitor of hepatocyte growth factor/c-MET, which is associated with sorafenib resistance. In the phase III CELESTIAL trial, in which over 700 patients with prior exposure to sorafenib and progressing hepatocellular carcinoma (HCC) were randomly assigned to cabozantinib or placebo, median overall survival was better with cabozantinib and the difference was especially pronounced when the analysis was limited to patients whose only prior therapy was sorafenib [24]. The most common grade 3 or 4 adverse events with cabozantinib were palmar-plantar erythrodysesthesia, hypertension increased aspartate aminotransferase, fatigue, and diarrhea. (See "Systemic treatment for advanced hepatocellular carcinoma", section on 'Cabozantinib'.)

Heated intraperitoneal chemotherapy of no benefit for isolated peritoneal carcinomatosis from metastatic colorectal cancer (July 2018)

Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) may be considered for patients with isolated peritoneal carcinomatosis from colorectal cancer (CRC), but the specific benefits of each component have not been addressed, particularly in the context of modern systemic combination chemotherapy. In the PRODIGE-7 trial, 265 patients with isolated peritoneal metastases from CRC were randomly assigned to CRS followed by HIPEC or CRS alone; 96 percent received systemic chemotherapy for six months prior to surgery, after surgery, or both [25]. The addition of HIPEC did not increase median overall survival or relapse-free survival, but nearly doubled the rate of severe 60-day postoperative morbidity. Randomized trials are needed to assess the benefit of CRS relative to systemic chemotherapy alone in this population. (See "Locoregional methods for management and palliation in patients who present with stage IV colorectal cancer", section on 'Randomized trials'.)

Adjuvant oxaliplatin in patients treated with neoadjuvant therapy for rectal cancer (July 2018)

The best regimen for postoperative adjuvant chemotherapy in patients who have received neoadjuvant therapy for rectal cancer is not established. In the randomized phase II ADORE trial, patients with curatively resected rectal cancer after neoadjuvant chemoradiotherapy and pathologic ypII (ypT3-4, ypN0) or III (ypT0-4, ypN1-2) stage disease were randomly assigned to four months of fluoropyrimidine-based versus oxaliplatin-containing chemotherapy [26]. The group assigned to oxaliplatin had a better six-year disease-free survival, although treatment-related toxicity was also higher, and the improvement in overall survival was modest. In exploratory subgroup analysis, patients with ypN2 stage III disease and those with minimally regressed tumors seemed to derive the most benefit from oxaliplatin. (See "Adjuvant therapy after neoadjuvant therapy for rectal cancer", section on 'Evidence'.)

Neoadjuvant therapy for potentially resectable pancreatic cancer (June 2018)

The role of neoadjuvant therapy in patients with potentially resectable pancreatic cancer is evolving. Limited data from two prospective trials support benefit of neoadjuvant therapy (gemcitabine in one trial; cisplatin, epirubicin, gemcitabine, and capecitabine in another) prior to resection over upfront surgery followed by adjuvant chemotherapy [27,28]. Neoadjuvant therapy appears to be a reasonable alternative to upfront surgery followed by adjuvant therapy in patients with potentially resectable pancreatic cancer whose performance and comorbidity status suggest they are likely to tolerate treatment. However, for the rare patient with a <2 a="" apparently="" as="" by="" class="medical medical_review" cm="" determined="" ee="" href="https://www.uptodate.com/contents/treatment-for-potentially-resectable-exocrine-pancreatic-cancer?sectionName=NEOADJUVANT+THERAPY&topicRef=8361&anchor=H2619094824&source=see_link#H2619094824" imaging="" is="" nbsp="" neoadjuvant="" node-negative="" not="" pretreatment="" probably="" style="background-color: transparent; color: #00905a;" therapy="" tumor="" warranted.="">"Treatment for potentially resectable exocrine pancreatic cancer", section on 'Neoadjuvant therapy'

CAPTEM for advanced pancreatic neuroendocrine tumors (June 2018)

Cytotoxic chemotherapy is an appropriate option for patients with an advanced pancreatic neuroendocrine tumor (pNET) whose disease is inadequately controlled on a long-acting somatostatin analog, and it is an alternative to sunitinib or everolimus for highly symptomatic or rapidly progressing patients. The optimal regimen is not established. In a phase II study that randomly assigned 144 patients with progressive unresectable or metastatic pNET to temozolomide (TEM) alone or capecitabine plus TEM (CAPTEM), combined therapy was associated with better progression-free and overall survival, and a higher disease control rate [29]. Serious adverse effects were twice as common with combined therapy; the most common were neutropenia, nausea and vomiting, diarrhea, and fatigue. These results establish CAPTEM as a reference regimen for advanced pNET. (See "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion", section on 'Dacarbazine (DTIC) and temozolomide-based regimens'.)

Serum vitamin D levels and risk of colorectal cancer (June 2018)

Poor vitamin D status has been associated with an increased risk of colon cancer. This association is supported by a recent analysis of participant-level data from 17 cohorts (5706 colorectal cancer cases and 7107 controls) [30]. Compared with 25(OH)D levels 20 to <25 class="nowrap" nbsp="" span="" style="white-space: nowrap;">ng/mL

(50 to <62 .5="" class="nowrap" nbsp="" span="" style="white-space: nowrap;">nmol/L), a 25(OH)D level <12 class="nowrap" nbsp="" span="" style="white-space: nowrap;">ng/mL (30 nmol/L) was associated with a higher risk of colorectal cancer, whereas 25(OH)D levels 30 to <40 class="nowrap" nbsp="" span="" style="white-space: nowrap;">ng/mL (75 to <100 class="nowrap" nbsp="" span="" style="white-space: nowrap;">nmol/L)were associated with a lower risk. It is not known if there is a causal relationship between vitamin D and cancer risk, however; data from current interventional studies of the protective effect of vitamin D supplementation on colorectal neoplasia are conflicting. Vitamin D levels of 30 to 40 ng/mL are within the accepted range for optimizing skeletal health. (See "Vitamin D and extraskeletal health", section on 'Cancer' and "Colorectal cancer: Epidemiology, risk factors, and protective factors", section on 'Vitamin D'.)

Posttreatment surveillance intensity not associated with earlier detection of recurrence or better survival in colorectal cancer (June 2018)

Intensive posttreatment surveillance using serum levels of carcinoembryonic antigen (CEA) and cross-sectional imaging of the torso is recommended for patients with resected stage II or III colorectal cancer (CRC) who would be candidates for curative intent surgery in the event of a disease recurrence. Two new studies have addressed testing frequency:

●The COLOFOL trial compared a high-intensity (CEA and computed tomography [CT] every six months for three years) versus low-intensity (CEA and CT at 12 and 36 months only) surveillance strategy in 2555 patients treated for stage II or III colon cancer [31]. The frequency of recurrence detection was similar in both groups as was five-year overall and cancer-specific mortality.

●A similar finding was noted in an analysis of data from the National Cancer Database, which was augmented by primary data on surveillance testing and disease recurrence from randomly selected patients treated between 2006 and 2007 at 1175 Commission on Cancer accredited facilities [32]. There were no significant differences in any key outcome (time to detection of recurrence, overall survival, likelihood of undergoing surgical resection for recurrence) for patients treated at facilities that utilized high- versus low-intensity imaging or CEA testing.

These studies suggest that imaging and CEA testing more often than yearly does little to improve survival after CRC resection and may result in a change of management guidelines from the various professional organizations. Until then, we still follow published guidelines, which all suggest monitoring CEA every three to six months, at least for the first two to three years, and annual cross-sectional imaging (table 2). (See "Surveillance after colorectal cancer resection", section on 'Intensive versus less intense surveillance strategies'.)

Oxaliplatin stop and go strategy with initial FOLFIRINOX for metastatic pancreatic cancer (June 2018)

The phase III ACCORD 11 trial established oxaliplatin, irinotecan, leucovorin, and short-term infusional fluorouracil (FOLFIRINOX) as a more effective but more toxic (hematologic, neuropathic) regimen over gemcitabine alone for first-line chemotherapy of patients with metastatic pancreatic cancer (MPC) who have a good performance status and a normal serum bilirubin level. In an attempt to mitigate neurotoxicity, the phase II PRODIGE35-PANOPTIMOX trial randomly assigned 275 patients with previously untreated MPC to six months of FOLFIRINOX versus four months of FOLFIRINOX, with responders switching to leucovorin-modulated fluorouracil maintenance treatment, and reintroduction of FOLFIRINOX at progression ("stop and go" strategy) [33]. Oncologic outcomes (six-month progression-free survival, median survival) were similar in both groups, and the median duration of fluorouracil/leucovorinmaintenance therapy was 4.5 months. Unexpectedly, rates of severe neurotoxicity were higher with maintenance therapy, although sensory neuropathy occurred later and was attributed to a higher cumulative oxaliplatin dose. These results support the discontinuation of oxaliplatin in patients who develop neuropathy after four months of standard FOLFIRINOX. We would continue with irinotecan, leucovorin, and short-term infusional fluorouracil (FOLFIRI) in this situation and, at the time of disease progression, switch to a different regimen rather than reintroduce oxaliplatin. (See "Chemotherapy for advanced exocrine pancreatic cancer", section on 'Oxaliplatin "stop and go" strategy'.)

Chemotherapy backbone for HER2-overexpressing advanced esophagogastric cancer (June 2018)

For patients with advanced human epidermal growth factor receptor 2 (HER2)-overexpressing esophagogastric adenocarcinomas, the addition of trastuzumab to cisplatin plus a fluoropyrimidine significantly improved survival in the phase III ToGA trial, although the optimal chemotherapy backbone is not established. A meta-analysis comparing different first-line trastuzumab-containing regimens in 15 published studies concluded that survival was better and treatment was less toxic when trastuzumab was combined with oxaliplatin plus a fluoropyrimidine compared with cisplatin plus a fluoropyrimidine [34]. For most patients receiving initial trastuzumab-containing chemotherapy, an oxaliplatin/fluoropyrimidine doublet is preferred over cisplatin/fluoropyrimidine. (See "Systemic therapy for locally advanced unresectable and metastatic esophageal and gastric cancer", section on 'Specific chemotherapy backbone'.)

Updated clinical practice guidelines for metastatic pancreatic cancer (June 2018)

The American Society of Clinical Oncology has published updated clinical practice guidelines for metastatic pancreatic cancer after initial chemotherapy [35]. They support use of an irinotecan plus fluorouracil-based regimen for second-line therapy in patients who retain a good performance status and favorable comorbidity after first-line treatment with gemcitabine plus nabpaclitaxel. Routine testing of the tumor for microsatellite instability/deficiencymismatch repair is recommended for patients who would be candidates for checkpoint inhibitor immunotherapy. Our recommendations are consistent with these revised guidelines. (See "Chemotherapy for advanced exocrine pancreatic cancer", section on 'Second-line therapy'.)

Ramucirumab extends survival in advanced hepatocellular cancer with high AFP level (June 2018)

Ramucirumab is a recombinant monoclonal antibody that binds to vascular endothelial growth factor receptor 2 (VEGFR-2), blocking receptor activation. The placebo-controlled REACH trial had suggested a potential survival benefit in a subset of patients with hepatocellular carcinoma (HCC) who were previously treated with sorafenib and had high serum levels of alfa-fetoprotein (AFP). In a preliminary report of the follow-up placebo-controlled REACH-2 trial, which was restricted to patients with AFP >400 ng/mL, second-line ramucirumab improved overall survival [36]. However, the magnitude of benefit over placebo alone was numerically less than that seen in the REACH trial high AFP subset (1.2 versus 3.6 months). The objective response rate with ramucirumab was low (5 versus 1 percent), but the overall disease control rate (objective response plus stable disease) was 60 percent (versus 39 percent with placebo). One potential advantage of ramucirumab over other molecularly targeted second-line therapies for HCC is the absence of hand-foot skin reaction. (See "Systemic treatment for advanced hepatocellular carcinoma", section on 'Ramucirumab'.)

Adjuvant chemotherapy for rectal cancer with a pathologic complete response after neoadjuvant chemoradiotherapy (May 2018)

There is a paucity of direct evidence to support benefit for adjuvant chemotherapy following neoadjuvant chemoradiotherapy for locally advanced rectal cancer, and particularly, whether there is benefit for those with no residual tumor in the surgical specimen. Two separate observational cohort studies using data from the National Cancer Database concluded that adjuvant chemotherapy was associated with improved all-cause survival (relative risk reduction of 50 to 76 percent) in those with a complete pathologic response following neoadjuvant chemoradiotherapy and surgery [37,38]. However, the magnitude of the survival benefit identified in this relatively favorable population of patients was inexplicably high and likely represents an overestimation of treatment effects based upon unassessed factors that could have influenced both the decision to offer postresection chemotherapy and all-cause survival [39]. We do not base our decision whether or not to pursue postoperative chemotherapy on pathologic response following neoadjuvant chemotherapy and radiation. (See "Adjuvant therapy after neoadjuvant therapy for rectal cancer", section on 'Can response to neoadjuvant therapy predict benefit?'.)

BRAF inhibitor plus cetuximab for RAS wild-type BRAF V600E-mutated metastatic colorectal cancer (May 2018)

Mutations in the BRAF V600E gene are associated with resistance to agents targeting the epidermal growth factor receptor (EGFR) in metastatic colorectal cancer (mCRC). Whether resistance can be overcome through the use of a BRAF inhibitor was addressed in the randomized phase III BEACON trial in patients with RAS wild-type BRAF V600E mutant progressive mCRC that compared cetuximab plus the BRAF inhibitor encorafenib (with or without the MEK inhibitor binimetinib) versus cetuximab plus irinotecan [40]. In a preliminary report of 30 patients who received encorafenib plus binimetinib and cetuximab during the safety lead-in of the trial, clinical activity was encouraging with an overall response rate of 41 percent, and at least one complete response. These results are consistent with previous findings supporting efficacy for a different BRAF inhibitor (vemurafenib) in combination with cetuximab and irinotecan compared with cetuximab and irinotecan alone in unresectable mCRC [41]. Although the data are not robust, the combination of vemurafenib plus an anti-EGFR agent and irinotecan is a reasonable option for second-line therapy in patients who have RAS wild-type but BRAF V600E mutant mCRC. (See "Systemic chemotherapy for nonoperable metastatic colorectal cancer: Treatment recommendations", section on 'RAS wild-type, BRAF mutated tumors'.)

Initial sorafenib versus nonsurgical liver-directed therapies for liver-limited hepatocellular cancer (April 2018)

Two new studies have addressed the relative benefit of initial systemic therapy versus nonsurgical liver-directed therapy in patients with liver-limited hepatocellular cancer (HCC) that is not amenable to resection, transplantation, or local ablation:

●A randomized trial involving 360 Asian patients with newly diagnosed unresectable HCC without portal vein thrombus or extrahepatic metastases (89 percent Child-Pugh A cirrhosis (table 3)) compared sorafenib with radioembolization using 90-Y microspheres; radioembolization provided a higher disease control rate with fewer adverse events [42].

●In a trial comparing transhepatic arterial chemoembolization (TACE) plus radiotherapy (RT) versus sorafenib in 90 patients with liver-confined HCC invading no more than the first or second branch of the portal vein, and Child-Pugh A cirrhosis, TACE/RT improved progression-free survival, radiographic response rates, and overall survival [43].

Given the more favorable side effect profile, locoregional forms of therapy such as TACE and radioembolization may be preferable to systemic therapy for initial treatment of unresectable liver-limited HCC in patients who are suitable candidates for such procedures. (See "Nonsurgical therapies for localized hepatocellular carcinoma: Transarterial embolization, radiation therapy, and radioembolization", section on 'Radioembolization versus sorafenib'.)

Treatment for Helicobacter pylori and risk of metachronous gastric cancer (March 2018)

Helicobacter pylori infection is a well-defined risk factor for gastric cancer. For patients who have undergone endoscopic resection of early gastric cancer and who have H. pylori infection, treatment for H. pylori appears to reduce the risk of subsequent cancer. In a single-center randomized trial including 396 patients who had undergone endoscopic resection for early gastric cancer or high-grade adenoma, patients treated for H. pylori infection were less likely to develop a metachronous cancer after a mean follow-up of six years compared with those given placebo (7 versus 13 percent) [44]. H. pylori eradication therapy is recommended for patients with early gastric cancer who are found to be infected. (See "Early gastric cancer: Treatment, natural history, and prognosis", section on 'Helicobacter pylori infection'.)

Nivolumab plus ipilimumab for microsatellite-unstable metastatic colorectal cancer (January 2018)

Previous trials in patients with metastatic colorectal cancer (mCRC) with high levels of microsatellite instability (MSI-H) or DNA mismatch repair deficiency (dMMR) have reported durable benefit from anti-programmed death-1 (PD-1) monotherapy with pembrolizumab or nivolumab. In the CheckMate-142 trial, patients who received the combination of nivolumab plus ipilimumab (which inhibits a different immune checkpoint) had a 55 percent response rate, and at 12 months, 71 percent remained progression-free [45]. Most adverse events were low grade. Indirect comparisons suggest that combined immunotherapy using ipilimumab and nivolumab provides improved efficacy over anti-PD-1 monotherapy and has a favorable benefit:risk ratio. Largely based on these data, in July 2018 the US Food and Drug Administration approved the combination of nivolumab plus ipilimulab for patients with previously treated MSI-M or dMMR mCRC. (See "Systemic chemotherapy for metastatic colorectal cancer: Completed clinical trials", section on 'Immune checkpoint inhibitors and mismatch repair deficient tumors' and "Systemic chemotherapy for nonoperable metastatic colorectal cancer: Treatment recommendations", section on 'Patients with microsatellite unstable/deficient mismatch repair tumors'.)

GENITOURINARY ONCOLOGY

Abiraterone added to enzalutamide not effective for metastatic castration-resistant prostate cancer (August 2018)

In the randomized PLATO trial, adding abiraterone acetate to enzalutamide did not improve progression-free survival (PFS) after prostate-specific antigen (PSA) progression in men on enzalutamide monotherapy for chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC) [46]. Hypertension and elevated liver enzymes were more common with combined therapy. (See "Castration-resistant prostate cancer: Treatments targeting the androgen pathway", section on 'Prior enzalutamide therapy'.)

Apalutamide and enzalutamide for nonmetastatic castration-resistant prostate cancer (July 2018)

Men with nonmetastatic castration-resistant prostate cancer, as manifested by a rising serum prostate-free antigen (PSA) despite androgen deprivation therapy (ADT), are at high risk for developing metastatic disease. Two phase III trials of androgen receptor antagonists, the PROSPER trial with enzalutamide [47] and the SPARTAN trial with apalutamide [48], demonstrated prolonged metastasis-free survival for the intervention compared with placebo. Largely based upon these results, both apalutamide and enzalutamide have been approved by the US Food and Drug Administration for treatment of nonmetastatic castration-resistant prostate cancer. (See "Castration-resistant prostate cancer: Treatments targeting the androgen pathway", section on 'Androgen receptor antagonists'.)

Radiation therapy for lung metastases in children with Wilms tumor (June 2018)

The optimal management for children with Wilms tumor with lung metastases is uncertain. Historically, most patients were treated with whole lung radiation therapy (RT). In a study of patients with favorable histology Wilms tumor and isolated lung metastases, use of lung RT was omitted if initial chemotherapy led to a complete lung nodule response [49]. Overall and event-free survival were superior to previous studies in which all patients received lung RT. These results suggest that the strategy of tailoring RT to the patient’s response to chemotherapy results in excellent outcomes and avoids long-term radiation-related toxicity in children with lung metastases. (See "Treatment and prognosis of Wilms tumor", section on 'Lung metastases'.)

Treatment of metastatic castration-sensitive prostate cancer (April 2018)

Multiple clinical trials have delineated the benefits and toxicities of combining androgen deprivation therapy (ADT) with either docetaxel or abiraterone compared with ADT alone for the initial treatment of men with metastatic castration-sensitive prostate cancer (CSPC). Based upon these trials, the American Society of Clinical Oncology (ASCO) has published guidelines for the treatment of metastatic CSPC [50]. Both ADT plus docetaxel and ADT plus abiraterone are preferred options compared with ADT alone for patients with high-volume CSPC and/or high risk for more rapid disease progression or death. There are no direct data comparing ADT plus docetaxel versus ADT plus abiraterone, and the choice of treatment should include a discussion with the patient about potential toxicities, duration of treatment, and costs. (See "Initial systemic therapy for castration-sensitive prostate cancer", section on 'Combined modality approaches incorporating ADT'.)

Multiparametric MRI in men with suspected prostate cancer (March 2018)

For men suspected of having prostate cancer based on either an elevated serum prostate-specific antigen (PSA) and/or abnormal digital rectal examination, transrectal ultrasound (TRUS)-guided biopsy has typically been performed for further evaluation. The use of multiparametric magnetic resonance imaging (mMRI), with or without targeted biopsy, was compared with TRUS-guided biopsy in the randomized PRECISION trial; biopsy was performed in the mMRI group for lesions that were suspicious for clinically significant prostate cancer (Gleason 3+4 or greater) and was not performed for MRI results not suggestive of prostate cancer [51]. Targeted biopsy based on mMRI detected an increased number of clinically significant prostate cancers and decreased the number of men undergoing biopsy. As access to mMRI and expertise in interpreting these studies increases, the role of this technology in prostate cancer diagnosis will likely increase. (See "The role of magnetic resonance imaging in prostate cancer", section on 'Lesion localization'.)

GYNECOLOGIC ONCOLOGY

Trastuzumab and chemotherapy for advanced or recurrent serous endometrial carcinoma (July 2018)

Standard treatment for women with advanced or recurrent serous endometrial cancer is chemotherapy, although novel strategies are under investigation for those whose tumors overexpress human epidermal growth factor receptor 2 (HER2). In a randomized phase II trial enrolling 61 such women, the addition of the anti-HER2 antibody trastuzumab to chemotherapy, compared with chemotherapy alone, improved median progression-free survival (12.6 versus 8.0 months), with no increase in toxicities [52]. Given these data, some UpToDate contributors assess HER2 expression in advanced or recurrent endometrial serous carcinomas, for possible incorporation of trastuzumab with chemotherapy, although this remains an off-label indication for trastuzumab. (See "Treatment of recurrent or metastatic endometrial cancer", section on 'Novel agents'.)

Pembrolizumab for recurrent or metastatic PD-L1 positive cervical cancer (July 2018)

For women with recurrent or metastatic cervical cancer, chemotherapy has been standard treatment, initially in combination regimens and, upon progression, as single agent treatment. However, in preliminary results of a phase II study, among 81 previously treated patients with advanced cervical cancer with programmed death-ligand 1 (PD-L1) expression of 1 percent or more, the objective response rate to the immune checkpoint inhibitor pembrolizumabwas 13 percent at a median follow-up of 10.3 months, and the median duration of response had not been reached [53]. For women who have experienced progression on prior chemotherapy for metastatic cervical cancer and desire further treatment, we now assess PD-L1 expression and offer pembrolizumab as an option if PD-L1 is expressed. (See "Management of recurrent or metastatic cervical cancer", section on 'Second-line therapy'.)

High rates of regression of cervical intraepithelial neoplasia, grade 2 (March 2018)

Management of high-grade cervical intraepithelial neoplasia (CIN 2 or 3) has evolved over time, and current guidelines encourage expectant management rather than conization for young women, based on high regression rates. In a meta-analysis including over 3000 women with untreated CIN 2 lesions managed conservatively, lesions regressed in 50 percent, persisted in 32 percent, and progressed in 18 percent at 24 months [54]. Regression rates were even higher in women younger than 30 years: lesions regressed in 60 percent, persisted in 23 percent, and progressed in 11 percent. Most cases of progression were to CIN 3+; there were 15 cases of cervical adenocarcinoma. This study provides the most robust data to date in support of expectant management of CIN 2, particularly for younger women. (See "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions", section on 'Risk of malignant disease'.)

HEAD AND NECK CANCER

Trials incorporating cetuximab plus radiation therapy for locally advanced squamous cell carcinoma of the head and neck (September 2018)

While epidermal growth factor receptor (EGFR) is highly overexpressed in head and neck squamous cell carcinoma (SCC), the role of the EGFR inhibitor cetuximab in locally advanced disease, particularly as a radiosensitizer, is under investigation. For example, in one randomized trial, the strategy of chemotherapy followed by concurrent cetuximab/radiotherapy demonstrated similar survival outcomes and lower rates of distant metastases compared with concurrent chemoradiotherapy, but with greater toxicity and treatment-related mortality [55]. In a second trial, concurrent cetuximab/radiotherapy was evaluated with or without concurrent carboplatin and 5FU [56]. While disease outcomes were improved with the addition of chemotherapy, rates of severe mucositis, feeding tube insertion, and hospitalization were higher. Importantly, as all patients in this trial received cetuximab, its contribution to both the efficacy and toxicities observed is unknown. Given available evidence, concurrent platinum-based chemoradiotherapy remains our preferred approach for most locally advanced SCC of the head and neck. We reserve cetuximab for patients with a good performance status who are not candidates for platinum-based regimens due to a specific contraindication (eg, nephrotoxicity, ototoxicity, or neuropathy). (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Induction plus concurrent chemotherapy versus concurrent chemotherapy alone'.)

MELANOMA AND OTHER SKIN CANCER

Global burden of melanoma attributable to UV radiation (August 2018)

Ultraviolet (UV) radiation is a known carcinogen and a recognized risk factor for melanoma and other skin cancers, especially in individuals with light complexion and poor tanning ability. A study aimed at quantifying the global population attributable fraction of melanomas due to UV radiation estimated that 168,000 new melanoma cases in 2012 were attributed to excess exposure to UV radiation, representing approximately 76 percent of all new melanoma cases worldwide [57]. This finding provides further support to the recommendation that individuals at increased risk of melanoma and those highly exposed to sunlight should be counseled about adopting sun protection measures, including wearing sun-protective clothing and applying a broad-spectrum sunscreen daily and thoroughly before going out during daylight hours. (See "Primary prevention of melanoma", section on 'Ultraviolet radiation'.)

Checkpoint inhibitor immunotherapy for advanced cutaneous squamous cell carcinoma (June 2018)

Therapeutic options are limited for patients with locally advanced or metastatic cutaneous squamous cell carcinoma. A phase I-II study with the experimental anti-programmed cell death-1 (PD-1) antibody cemiplimab found a 47 percent objective response rate in patients with metastatic disease, with more than 80 percent still responding at the time of data cutoff [58]. While checkpoint inhibitor immunotherapy for advanced cutaneous squamous cell carcinoma remains experimental, these findings are promising for this therapeutic approach. (See "Systemic treatment of advanced cutaneous squamous and basal cell carcinomas", section on 'Checkpoint inhibitor immunotherapy'.)

Adjuvant immunotherapy with pembrolizumab for cutaneous melanoma (April 2018)

Patients with cutaneous melanoma and positive lymph nodes (stage III) at initial definitive surgery are at increased risk for recurrence and subsequent death due to metastatic melanoma (table 4A-B). In a phase III trial, pembrolizumab, a checkpoint inhibitor targeting programmed cell death protein 1 (PD-1), increased recurrence-free survival compared with placebo, with a level of activity similar to that of nivolumab in the adjuvant setting [59]. Immunotherapy targeting PD-1 remains the preferred approach for patients with resected stage III melanoma. Results are similar for pembrolizumab and nivolumab; nivolumab, but not pembrolizumab, is approved by the US Food and Drug Administration for this indication. (See "Adjuvant therapy for cutaneous melanoma", section on 'Pembrolizumab'.)

NEUROONCOLOGY

Targeted therapies in development for recurrent glioblastoma (June 2018)

A variety of promising systemic and local therapies are in development for recurrent glioblastoma. Preliminary phase II trial results suggest that the intravenous antibody-drug conjugate depatuxizumab mafodotin (composed of an anti-epidermal growth factor receptor [EGFR] monoclonal antibody conjugated to an inhibitor of tubulin polymerization) plus temozolomide improves survival compared with lomustine plus temozolomide in patients with recurrent EGFR-amplified glioblastoma (one-year overall survival 40 versus 28 percent) [60]. Some genetically engineered local viral therapies, such as a recombinant oncolytic poliovirus and vocimagene amiretrorepvec, which introduces a suicide gene into malignant cells, have also been associated with an encouraging number of durable responses in early-phase studies [61,62]. (See "Management of recurrent high-grade gliomas", section on 'Experimental therapies' and "Overview of gene therapy, gene editing, and gene silencing", section on 'Cancer therapy'.)

Cancer predisposition syndromes in patients with medulloblastoma (June 2018)

Medulloblastoma has been observed in association with several rare cancer predisposition syndromes, but the full spectrum of genetic risk has not been well characterized. In a study that analyzed clinical and molecular genetic data on more than 1000 patients with medulloblastoma, 6 percent of patients had a germline pathogenic variant in one of six cancer predisposition genes: TP53 (Li-Fraumeni syndrome); PTCH1 or SUFU (Gorlin syndrome); APC(familial adenomatous polyposis); and BRCA2 or PALB2 (hereditary breast and ovarian cancer syndromes) [63]. The prevalence of a predisposing mutation was highest in patients with sonic hedgehog (SHH) subgroup tumors. More than half of patients had no family history or clinical signs of a cancer predisposition syndrome. Guidelines for genetic testing and counseling in patients with medulloblastoma are proposed based on these findings. (See "Histopathology, genetics, and molecular subgroups of medulloblastoma", section on 'Genetic predisposition'.)

Early experience with checkpoint inhibitors in recurrent glioblastoma (May 2018)

Although multiple trials are testing various forms of immunotherapy in patients with glioblastoma, published data remain limited. In a phase I trial investigating the safety of monotherapy or combination therapy with two checkpoint inhibitors, nivolumab (a programmed death 1 [PD-1] inhibitor) with and without ipilimumab (an anti-cytotoxic T-lymphocyte antigen 4 [CTLA4] antibody), in 40 patients with recurrent glioblastoma, nivolumab monotherapy was better tolerated than combination therapy, and a partial response was seen in three patients (one treated with monotherapy, two with combination therapy) [64]. An additional eight patients had stable disease for ≥12 weeks (two treated with nivolumab monotherapy). PD-1 ligand expression did not correlate with clinical response. Further studies are needed to help select patients most likely to respond to checkpoint inhibitor immunotherapy. (See "Management of recurrent high-grade gliomas", section on 'Experimental therapies'.)

PALLIATIVE AND SUPPORTIVE CARE

High prevalence of potentially unsafe zolpidem dosing (September 2018)

Zolpidem is a widely prescribed nonbenzodiazepine hypnotic with increasingly recognized variability in metabolism and next-morning drug levels and side effects, particularly in women and older adults. In 2013, the US Food and Drug Administration issued safety warnings that included lowering of the recommended dose of zolpidem in women to 5 mg for immediate release products and 6.25 mg for extended release products. Importantly, despite these warnings, a large database study in the United States found that in the year 2015 among 3.8 million zolpidem users, 64 percent of older adults and 68 percent of women reported taking higher than the recommended dose of zolpidem [65]. In addition, 41 percent of patients reported concurrent sustained use of one or more other central nervous system depressants (eg, opioids, benzodiazepines). Clinicians should remain vigilant to potentially unsafe dosing of zolpidem in current users; recommended doses for zolpidem and related hypnotics are listed in the table (table 5). (See "Behavioral and pharmacologic therapies for chronic insomnia in adults", section on 'Dosing precautions'.)

Talc plus indwelling catheter for malignant pleural effusion (April 2018)

The combination of an indwelling catheter and pleurodesis as initial therapy for outpatients with recurrent malignant pleural effusion (MPE) is unstudied. In a randomized trial of over 150 patients with MPE, patients in the group assigned to an indwelling catheter plus talc (via the catheter) had fewer symptoms and higher success rates of pleurodesis compared with the indwelling catheter group [66]. However, high rates of patient exclusion from trial participation and inadequate duration of thoracentesis alone prior to indwelling catheter placement suggest that only select patients are suitable. Nonetheless, the ability to perform talc pleurodesis via an indwelling catheter as an outpatient is appealing and may be a reasonable option in patients with MPE. (See "Management of malignant pleural effusions", section on 'Talc pleurodesis PLUS an indwelling catheter'.)

Chronic opioid therapy and infection risk (April 2018)

In preclinical studies, some opioids have immunosuppressive properties, and epidemiologic studies have reported an association between prescription opioid use and serious infection. In a case control study in a state Medicaid population, over 1200 patients with laboratory-confirmed invasive pneumococcal disease were matched to 24,300 controls [67]. After adjusting for several potential confounders, individuals with invasive pneumococcal disease had a 62 percent greater odds of being current opioid users. Associations were strongest for long-acting opioids, high-potency opioids (morphine, codeine, oxycodone, hydromorphone, fentanyl), and higher opioid doses. Additional research is needed to elucidate the comparative risk with individual opioids. (See "Prevention and management of side effects in patients receiving opioids for chronic pain", section on 'Infection risk'.)

SOFT TISSUE AND BONE TUMORS

Maintenance chemotherapy in rhabdomyosarcoma (June 2018)

Outcomes for children with intermediate-risk rhabdomyosarcoma (RMS) have remained virtually unchanged over the past two decades despite intensification of alkylating agents and addition of new therapies such as topotecan. A recent randomized trial by the European Paediatric Soft Tissue Sarcoma Study Group (EPSTSSG) in patients age 6 months to 21 years with node-negative alveolar or incompletely resected (group II or III) embryonal RMS arising in an unfavorable site (head and neck, pelvis) or lymph node-positive disease, and no radiologic evidence of disease at the end of treatment (typically six to eight months of intense chemotherapy, surgery, and/or radiation therapy) compared maintenance therapy (weekly intravenous vinorelbine plus daily oral cyclophosphamide for six months) with no maintenance therapy [68]. Maintenance therapy was associated with borderline significant improvement in three-year event-free survival and significantly better three-year overall survival. However, the treatment schema in this European study differs from that generally used in the United States (the Children’s Oncology Group [COG] protocol involves a longer duration of therapy and inclusion of all patients in the outcome analysis regardless of remission status at the end of treatment). Thus, while the authors of the European study suggested that maintenance therapy be incorporated as standard of care, we believe that maintenance therapy is a reasonable approach for children treated according to the EPSTSSG guidelines, but that the trial results cannot be extrapolated or incorporated into the standard therapy regimen for patients treated according to COG guidelines. (See "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment", section on 'Role of maintenance chemotherapy'.)

THORACIC ONCOLOGY

Atezolizumab plus bevacizumab and chemotherapy in advanced, nonsquamous NSCLC (July 2018)

Although combinations of chemotherapy and immunotherapy are being explored for advanced non-small cell lung cancer (NSCLC), previous trials have typically excluded patients with ALK or EGFR driven cancers. In the IMpower 150 trial, among patients with advanced, chemotherapy-naïve, nonsquamous NSCLC, addition of the anti-PD-L1 antibody atezolizumab to bevacizumab and a platinum-based chemotherapy doublet improved progression-free survival, a benefit that was also observed in the 14 percent whose tumors had activating ALK or EGFR mutations [69]. Based on these new data, the combination of immunotherapy and chemotherapy may be considered for those with driver-mutated nonsquamous NSCLC who have progressed on available targeted therapies, although this remains an off-label indication. (See "Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer", section on 'Resistance to other ALK inhibitors'.)

Bioengineered tracheobronchial reconstruction using stented aortic matrices (June 2018)

Large proximal tumors of the trachea or proximal bronchus are generally considered inoperable, and treatment is mostly palliative. A recent study described the outcomes of 13 patients with tracheobronchial lesions who underwent radical resection followed by airway reconstruction with a novel technique that used cryopreserved aortic allografts and stenting to generate a new airway [70]. At 90 days, there were no deaths and no adverse events related to the surgery. Stents were removed at about 18 months and at four years, 79 percent of patients remained alive, the majority of whom were able to breathe through their newly formed airway. This technique remains investigational but offers future promise to those with inoperable tracheobronchial lesions. (See "Clinical presentation, diagnostic evaluation, and management of central airway obstruction in adults", section on 'Investigational'.)

Lung cancer incidence among young men and women (May 2018)

Lung cancer incidence has historically been higher in men than women. However, a study using 20 years of data from a United States cancer registry found that, although the overall incidence of lung cancer has generally decreased among both men and women 30 to 54 years old, the incidence of lung cancer in non-Hispanic whites in the 30- to 49-year-old age group is now higher in women than in men [71]. This reversal in trends is not fully explained by gender differences in smoking behaviors. More study is required to understand the reasons for the relatively higher incidence of lung cancer among young women compared with young men. (See "Women and lung cancer", section on 'Comparison of men and women'.)

Immunotherapy for advanced, chemotherapy-naïve NSCLC (April 2018)

Phase III trials are evaluating the role of immunotherapies, including antibodies against programmed death-ligand 1 (PD-L1), programmed death receptor-1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) in the frontline management of advanced non-small cell lung cancer (NSCLC):

●In separate trials evaluating either squamous (KEYNOTE 407) or nonsquamous (KEYNOTE 189) PD-L1 unselected, advanced NSCLC, the addition of the anti-PD-1 antibody pembrolizumab to standard chemotherapy improved both progression-free survival (PFS) and overall survival (OS) outcomes, with no increase in severe adverse events [72,73].

●While previous evidence had demonstrated improvements with pembrolizumab monotherapy over chemotherapy for those with ≥50 percent tumor PD-L1 expression (KEYNOTE-024) [74], a newer trial (KEYNOTE-042) has shown OS improvements for those with any degree of tumor PD-L1 expression [75].

●In CheckMate 227, among patients with advanced NSCLC and PD-L1 expression of at least 1 percent, the combination of the anti-PD-1 antibody nivolumab and the anti-CTLA-4 antibody ipilimumab improved PFS among those with a high tumor mutational burden, compared with chemotherapy [76].

Based on available data, for those in whom at least 50 percent of tumor cells stain for PD-L1, we treat with pembrolizumab monotherapy. For those with lesser or absent PD-L1 expression, we suggest the combination of pembrolizumab with platinum-based chemotherapy, given the improved likelihood of benefit over either strategy alone.

We await further data to determine the role of nivolumab and ipilimumab in the frontline management of advanced NSCLC. (See "Immunotherapy of advanced non-small cell lung cancer with immune checkpoint inhibition", section on 'Pembrolizumab in combination with chemotherapy'.)

Frontline osimertinib in EGFR-mutant, advanced NSCLC (April 2018)

Osimertinib is an oral third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). In a phase III randomized trial in over 550 treatment-naïve patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC), osimertinib was compared with standard of care (SOC) EGFR-TKI (gefitinib or erlotinib) [77]. Osimertinib improved progression-free survival (18.9 versus 10.2 months) and duration of response with fewer ≥grade 3 toxicities. Overall survival results are premature. Based on these data, the US Food and Drug Administration approved osimertinib for the frontline treatment of advanced NSCLC with an activating EGFR mutation [78], and we suggest its use in this setting. (See "Systemic therapy for advanced non-small cell lung cancer with an activating mutation in the epidermal growth factor receptor", section on 'Osimertinib in the front-line setting'.)

Immunotherapy in nonmetastatic NSCLC (March 2018)

Immunotherapy has already shaped the management of metastatic non-small cell lung cancer (NSCLC), and its use in earlier stage disease is also being evaluated:

●In a phase III trial of over 700 patients with unresectable stage III NSCLC without progression after completion of platinum-based chemoradiotherapy, the programmed death-ligand 1 (PD-L1) antibody durvalumab improved median progression-free and overall survival relative to placebo, with comparable rates of severe adverse events [79,80].

●In a pilot study of 21 patients with untreated, surgically resectable NSCLC, two doses of the programmed death receptor-1 (PD-1) antibody nivolumab administered prior to surgery resulted in a major pathologic response in 10 patients, with no treatment-related surgical delays [81].

The US Food and Drug Administration (FDA) approved durvalumab for patients with unresectable stage III NSCLC whose disease has not progressed following concurrent platinum-based chemoradiotherapy [82], and we now recommend its use in this setting. For patients with resectable disease, neoadjuvant nivolumab remains investigational. (See "Systemic therapy in resectable non-small cell lung cancer", section on 'Neoadjuvant immunotherapy' and "Management of stage III non-small cell lung cancer", section on 'Immunotherapy'.)

OTHER ONCOLOGY

Sodium thiosulfate for prevention of cisplatin ototoxicity in children (June 2018)

Cisplatin-related ototoxicity can be particularly severe in children. A prior randomized trial suggested potential benefit for preventive sodium thiosulfate (STS), but there were concerns that reported cancer outcomes might have been compromised. In the randomized phase III SIOPEL-6 trial in children receiving cisplatin for hepatoblastoma, a single dose of STS after each cisplatin dose was compared with no STS [83]. Children in the STS group had a lower incidence of hearing loss and similar cancer outcomes (three-year event-free survival, overall survival) compared with the control group. For children receiving cisplatin chemotherapy for average-risk hepatoblastoma, we suggest the addition of STS to reduce the risk of ototoxicity. The available evidence is insufficient to support the routine use of STS in children receiving cisplatin for treatment of other malignancies, or for adults receiving cisplatin. (See "Overview of neurologic complications of platinum-based chemotherapy", section on 'Prevention'.)

Checkpoint inhibitor immunotherapy in older adults (May 2018)

The use of checkpoint inhibitor immunotherapy has been a major advance in the treatment of a wide range of malignancies. Clinical trials demonstrating the benefits and side effects of this approach have been conducted in relatively young and fit patients. A meta-analysis of 5458 patients in nine randomized trials that compared nivolumab, pembrolizumab, or atezolizumab versus chemotherapy or targeted therapy in solid tumors found that checkpoint inhibitor immunotherapy appeared to have similar efficacy and toxicity in those ≥65 years versus those <65 a="" age="" class="abstract_t" href="https://www.uptodate.com/contents/whats-new-in-oncology/abstract/84" of="" style="background-color: transparent; color: #00905a;" years="">84

]. Chronologic age alone should not preclude the use of these agents. (See "Patient selection criteria and toxicities associated with checkpoint inhibitor immunotherapy", section on 'Elderly patients'.)

Updated NCI common terminology criteria for adverse events (March 2018)

The National Cancer Institute (NCI) Cancer Evaluation Treatment Program (CTEP) publishes standardized definitions to describe the severity of organ toxicity for patients receiving cancer therapy, known as the Common Terminology Criteria for Adverse Events (CTCAE, also called "common toxicity criteria" [CTC]). These criteria are used to assess toxicity and guide dose adjustments. An updated version (v5.0) of the CTCAE, effective April 1, 2018, has been released [85]. Selected tables from the CTCAE document and links to topics that address management of these adverse events are included in UpToDate. (See "Common terminology criteria for adverse events", section on 'Introduction'.)

Management guidelines for rheumatologic toxicities of checkpoint inhibitor immunotherapies for malignancy (March 2018)

Several expert groups, including the American Society of Clinical Oncology (in collaboration with the National Comprehensive Cancer Network) and the Society for Immunotherapy of Cancer, have developed guidelines for the evaluation and management of immune-related adverse events in patients receiving immune checkpoint inhibitor therapy for malignancy [86,87]. These guidelines include detailed recommendations for the evaluation and management of musculoskeletal toxicities, including inflammatory arthritis, myositis, and polymyalgia-like syndrome, as well as for the other organ systems affected by these agents. Our approach is generally consistent with the recommendations of both of these groups. (See "Rheumatologic complications of checkpoint inhibitor immunotherapy", section on 'Guidelines of major organizations'.)

REFERENCES

Hershman DL, Unger JM, Greenlee H, et al. Effect of Acupuncture vs Sham Acupuncture or Waitlist Control on Joint Pain Related to Aromatase Inhibitors Among Women With Early-Stage Breast Cancer: A Randomized Clinical Trial. JAMA 2018; 320:167.
Wolff AC, Hammond MEH, Allison KH, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol 2018; 36:2105.
Sparano JA, Gray RJ, Makower DF, et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2018; 379:111.
Earl HM, Hiller L, Vallier A-L, et al. PERSEPHONE: 6 versus 12 months (m) of adjuvant trastuzumab in patients (pts) with HER2 positive (+) early breast cancer (EBC): Randomised phase 3 non-inferiority trial with definitive 4-year (yr) disease-free survival (DFS) results. J Clin Oncol 2018; 36S: ASCO#506.
Francis PA, Pagani O, Fleming GF, et al. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med 2018; 379:122.
Gnant M, Pfeiler G, Steger GG, et al. Adjuvant denosumab in early breast cancer: Disease-free survival analysis of 3,425 postmenopausal patients in the ABCSG-18 trial. J Clin Oncol 2018; 36S: ASCO #500.
Coleman RE, Finkelstein D, Barrios CH, et al. Adjuvant denosumab in early breast cancer: First results from the international multicenter randomized phase III placebo controlled D-CARE study. J Clin Oncol 2018; 36S: ASCO #501.
Loibl S, O'Shaughnessy J, Untch M, et al. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol 2018; 19:497.
Wapnir IL, Price KN, Anderson SJ, et al. Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial. J Clin Oncol 2018; 36:1073.
Pivot X. Adjuvant chemotherapy for local relapse breast cancer. Lancet Oncol 2014; 15:125.
Braithwaite D, Miglioretti DL, Zhu W, et al. Family History and Breast Cancer Risk Among Older Women in the Breast Cancer Surveillance Consortium Cohort. JAMA Intern Med 2018; 178:494.
Pedersen SA, Gaist D, Schmidt SAJ, et al. Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol 2018; 78:673.
US Preventive Services Task Force, Grossman DC, Curry SJ, et al. Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2018; 319:1901.
Click B, Pinsky PF, Hickey T, et al. Association of Colonoscopy Adenoma Findings With Long-term Colorectal Cancer Incidence. JAMA 2018; 319:2021.
Colorectal cancer screening for average‐risk adults: 2018 guideline update from the American Cancer Society https://onlinelibrary.wiley.com/doi/abs/10.3322/caac.21457 (Accessed on May 30, 2018).
Hadjiliadis D, Khoruts A, Zauber AG, et al. Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations. Gastroenterology 2018; 154:736.
US Preventive Services Task Force, Grossman DC, Curry SJ, et al. Screening for Ovarian Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2018; 319:588.
Overman MJ, Ferrarotto R, Raghav K, et al. The Addition of Bevacizumab to Oxaliplatin-Based Chemotherapy: Impact Upon Hepatic Sinusoidal Injury and Thrombocytopenia. J Natl Cancer Inst 2018; 110:888.
Aranda E, García-Alfonso P, Benavides M, et al. First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: Phase II randomised MACRO2 TTD study. Eur J Cancer 2018; 101:263.
Pietrantonio F, Morano F.Corallo S, et al. First-line FOLFOX plus panitumumab (Pan) followed by 5FU/LV plus Pan or single-agent Pan as maintenance therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC): The VALENTINO study (abstract). J Clin Oncol 36, 2018 (suppl; abstr 3505). Abstract available online at https://meetinglibrary.asco.org/record/158738/abstract (Accessed on July 19, 2018).
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm606799.htm (Accessed on July 30, 2018).
www.cookmedical.com/products/35a4a7f2-867b-4c81-a983-44ea06277852 (Accessed on July 31, 2018).
Conroy T, Hammel P, Hebbar M, et al. Unicancer GI PRDIGE 24/CCTG PA.6 trial: A multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine in patients with resected pancreatic ductal adenocarcinomas (abstract). J Clin Oncol 36, 2018 (suppl; abstr LBA4001). Abstract available online at https://meetinglibrary.asco.org/record/159164/abstract (Accessed on June 15, 2018).
Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med 2018; 379:54.
Quenet F, Elias D, Roca L, et al. A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7 (abstract). J Clin Oncol 36, 2018 (suppl; abstr LBA3503). Abstract available online at https://meetinglibrary.asco.org/record/158740/abstract (Accessed on July 16, 2018).
Hong YS, Kim SY, Lee JS, et al. Long-term results of the ADORE trial: Adjuvant oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) versus 5-fluorouracil and leucovorin (FL) after preoperative chemoradiotherapy and surgery for locally advanced rectal cancer (abstract). J Clin Oncol 36, 2018 (suppl; abstr 3501). Abstract available online at https://meetinglibrary.asco.org/record/158736/abstract (Accessed on June 26, 2018).
Van Tienhoven G, Versteijne E, Suker M, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1) : A randomized, controlled, multicenter phase III trial (abstract). J Clin Oncol 36, 2018 (suppl; abstr LBA4002). Abstract available online at https://meetinglibrary.asco.org/record/160063/abstract (Accessed on June 15, 2018).
Reni M, Balzano G, Zanon S, et al. Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial. Lancet Gastroenterol Hepatol 2018; 3:413.
Kunz PL, Catalano PJ, Nimeiri H, et al. A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: A trial of the ECOG-ACRIN Cancer Research Group (E2211) (abstract). J Clin Oncol 36, 2018 (suppl; abstr 4004). Abstract available online at https://meetinglibrary.asco.org/record/160190/abstract (Accessed on June 19, 2018).
McCullough ML, Zoltick ES, Weinstein SJ, et al. Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts. J Natl Cancer Inst 2018.
Wille-Jørgensen P, Syk I, Smedh K, et al. Effect of More vs Less Frequent Follow-up Testing on Overall and Colorectal Cancer-Specific Mortality in Patients With Stage II or III Colorectal Cancer: The COLOFOL Randomized Clinical Trial. JAMA 2018; 319:2095.
Snyder RA, Hu CY, Cuddy A, et al. Association Between Intensity of Posttreatment Surveillance Testing and Detection of Recurrence in Patients With Colorectal Cancer. JAMA 2018; 319:2104.
Dahan L, Phelip JM, Le Malicot, et al. FOLFIRINOX until progression, FOLFIRINOX with maintenance treatment, or sequential treatment with gemcitabine and FOLFIRI.3 for first-line treatment of metastatic pancreatic cancer: A randomized phase II trial (PRODIGE 35-PANOPTIMOX) (abstract). J Clin Oncol 36, 2018 (suppl; abstr 4000). Abstract available online at https://meetinglibrary.asco.org/record/159166/abstract (Accessed on June 20, 2018).
Ter Veer E, Creemers A, de Waal L, et al. Comparing cytotoxic backbones for first-line trastuzumab-containing regimens in human epidermal growth factor receptor 2-positive advanced oesophagogastric cancer: A meta-analysis. Int J Cancer 2018; 143:438.
Sohal DPS, Kennedy EB, Khorana A, et al. Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol 2018; 36:2545.
Zhu AX, Kang Y-K, Yen C-J, et al. REACH-2: A randomized, double-blind, placebo-controlled phase 3 study of ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein (AFP) following first-line sorafenib (abstract). J Clin Oncol 36, 2018 (suppl; abstr 4003). Abstract available online at https://meetinglibrary.asco.org/record/159169/abstract (Accessed on June 19, 2018).
Dossa F, Acuna SA, Rickles AS, et al. Association Between Adjuvant Chemotherapy and Overall Survival in Patients With Rectal Cancer and Pathological Complete Response After Neoadjuvant Chemotherapy and Resection. JAMA Oncol 2018; 4:930.
Polanco PM, Mokdad AA, Zhu H, et al. Association of Adjuvant Chemotherapy With Overall Survival in Patients With Rectal Cancer and Pathologic Complete Response Following Neoadjuvant Chemotherapy and Resection. JAMA Oncol 2018; 4:938.
Chang GJ. Is There Validity in Propensity Score-Matched Estimates of Adjuvant Chemotherapy Effects for Patients With Rectal Cancer? JAMA Oncol 2018; 4:921.
Van Cutsem E, Cuyle P-J, Huijberts S, et al. BEACON CRC study safety lead-in (SLI) in patients with BRAFV600E metastatic colorectal cancer (mCRC): Efficacy and tumor markers (abstract). J Clini Oncol 36,2018 (suppl 4S; abstr 627). Abstract available online at https://meetinglibrary.asco.org/record/155628/abstract (Accessed on January 30, 2018).
Kopetz S, McDonough SL, Lenz H-J, et al. Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG S1406) (abstract). J Clin Oncol 35, 2017 (suppl; abstr 3505). Abstract available online at http://abstracts.asco.org/199/AbstView_199_194502.html (Accessed on July 24, 2017).
Chow PKH, Gandhi M, Tan SB, et al. SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma. J Clin Oncol 2018; 36:1913.
Yoon SM, Ryoo BY, Lee SJ, et al. Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Randomized Clinical Trial. JAMA Oncol 2018; 4:661.
Choi IJ, Kook MC, Kim YI, et al. Helicobacter pylori Therapy for the Prevention of Metachronous Gastric Cancer. N Engl J Med 2018; 378:1085.
Overman MJ, Lonardi S, Wong KYM, et al. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol 2018; 36:773.
Attard G, Borre M, Gurney H, et al. Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment. J Clin Oncol 2018; 36:2639.
Hussain M, Fizazi K, Saad F, et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med 2018; 378:2465.
Smith MR, Saad F, Chowdhury S, et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med 2018; 378:1408.
Dix DB, Seibel NL, Chi YY, et al. Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children's Oncology Group AREN0533 Study. J Clin Oncol 2018; 36:1564.
Morris MJ, Rumble RB, Basch E, et al. Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2018; 36:1521.
Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med 2018; 378:1767.
Fader AN, Roque DM, Siegel E, et al. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. J Clin Oncol 2018; 36:2044.
Chung HC, Schellens JHM, Delord JP, Perets R. Pembrolizumab treatment of advanced cervical cancer: Updated results from the phase 2 KEYNOTE-158 study. ASCO 2018; 36S: ASCO #5522.
Tainio K, Athanasiou A, Tikkinen KAO, et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ 2018; 360:k499.
Geoffrois L, Martin L, De Raucourt D, et al. Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial. J Clin Oncol 2018; :JCO2017762591.
Tao Y, Auperin A, Sire C, et al. Improved Outcome by Adding Concurrent Chemotherapy to Cetuximab and Radiotherapy for Locally Advanced Head and Neck Carcinomas: Results of the GORTEC 2007-01 Phase III Randomized Trial. J Clin Oncol 2018; :JCO2017762518.
Arnold M, de Vries E, Whiteman DC, et al. Global burden of cutaneous melanoma attributable to ultraviolet radiation in 2012. Int J Cancer 2018; 143:1305.
Migden MR, Rischin D, Schmults CD, et al. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med 2018; 379:341.
Eggermont AMM, Blank CU, Mandala M, et al. Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med 2018; 378:1789.
Van Den Bent, French P, Eoli M, et al. Updated results of the INTELLANCE 2/EORTC trial 1410 randomized phase II study on Depatux-M alone, Depatux-M in combination with temozolomide (TMZ) and either TMZ or lomustine (LOM) in recurrent EGFR amplified glioblastoma (NCT02343406). J Clin Oncol 2018; 36:suppl (Abstr # 2023).
Cloughesy TF, Landolfi J, Vogelbaum MA, et al. Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC. Neuro Oncol 2018; 20:1383.
Desjardins A, Gromeier M, Herndon JE 2nd, et al. Recurrent Glioblastoma Treated with Recombinant Poliovirus. N Engl J Med 2018; 379:150.
Waszak SM, Northcott PA, Buchhalter I, et al. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. Lancet Oncol 2018; 19:785.
Omuro A, Vlahovic G, Lim M, et al. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Neuro Oncol 2018; 20:674.
Moore TJ, Mattison DR. Assessment of Patterns of Potentially Unsafe Use of Zolpidem. JAMA Intern Med 2018; 178:1275.
Bhatnagar R, Keenan EK, Morley AJ, et al. Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion. N Engl J Med 2018; 378:1313.
Wiese AD, Griffin MR, Schaffner W, et al. Opioid Analgesic Use and Risk for Invasive Pneumococcal Diseases: A Nested Case-Control Study. Ann Intern Med 2018; 168:396.
Bisogno G, De Salvo GL, Bergeron C, et al. Maintenance low-dose chemotherapy in patients with high-risk (HR) rhabdomyosarcoma (RMS): A report from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) (abstract). J Clin Oncol 36, 2018 (suppl; abstr LBA2). Abstract available online at https://meetinglibrary.asco.org/record/161695/abstract (Accessed on June 21, 2018).
Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med 2018; 378:2288.
Martinod E, Chouahnia K, Radu DM, et al. Feasibility of Bioengineered Tracheal and Bronchial Reconstruction Using Stented Aortic Matrices. JAMA 2018; 319:2212.
Jemal A, Miller KD, Ma J, et al. Higher Lung Cancer Incidence in Young Women Than Young Men in the United States. N Engl J Med 2018; 378:1999.
Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med 2018; 378:2078.
Paz-Ares L, Luft A, Tafreshi A, et al. Phase 3 study of carboplatin-paclitaxel/nab-paclitaxel (Chemo) with or without pembrolizumab (Pembro) for patients with metastatic squamous (Sq) non-small cell lung cancer (NSCLC). J Clin Oncol 2018; 36S: ASCO #105.
Brahmer J, Rodriguez-Abreu D, Robinson A, et al. OA 17.06 Updated analysis of KEYNOTE-024: Pembrolizumab vs platinum-based chemotherapy for advanced NSCLC with PD-L1 TPS ≥50%. J Thorac Oncol 2017; 12:S1793.
Lopes G, Wu YL, Kudaba I, Kowalski D. Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: Open-label, phase 3 KEYNOTE-042 study. J Clin Oncol 2018; 36S: ASCO #LBA4.
Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med 2018; 378:2093.
Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2018; 378:113.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208065s008lbl.pdf (Accessed on April 23, 2018).
Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med 2017; 377:1919.
Antonia SJ, Villegas A, Daniel D, Vicente D. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med 2018; epub 9/25/18.
Forde PM, Chaft JE, Smith KN, et al. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med 2018; 378:1976.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761069s002lbl.pdf (Accessed on February 28, 2018).
Brock PR, Maibach R, Childs M, et al. Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. N Engl J Med 2018; 378:2376.
Elias R, Giobbie-Hurder A, McCleary NJ, et al. Efficacy of PD-1 & PD-L1 inhibitors in older adults: a meta-analysis. J Immunother Cancer 2018; 6:26.
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm (Accessed on March 28, 2018).
Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2018; 36:1714.
Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer 2017; 5:95.

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