Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update.

PURPOSE: To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to update the 2020 guideline on systemic therapy for HCC. The panel updated the systematic review to include randomized controlled trials (RCTs) published through October 2023 and updated recommendations. RESULTS: Ten new RCTs met the inclusion criteria and were added to the evidence base. RECOMMENDATIONS: Atezolizumab + bevacizumab (atezo + bev) or durvalumab + tremelimumab (durva + treme) may be offered first-line for patients with advanced HCC, Child-Pugh class A liver disease, and Eastern Cooperative Oncology Group performance status 0-1. Where there are contraindications to these therapies, sorafenib, lenvatinib, or durvalumab may be offered first-line. Following first-line treatment with atezo + bev, second-line therapy with a tyrosine kinase inhibitor (TKI), ramucirumab (for patients with alpha-fetoprotein [AFP] ≥400 ng/mL), durva + treme, or nivolumab + ipilimumab (nivo + ipi) may be recommended for appropriate candidates. Following first-line therapy with durva + treme, second-line therapy with a TKI is recommended. Following first-line treatment with sorafenib or lenvatinib, second-line therapy options include cabozantinib, regorafenib for patients who previously tolerated sorafenib, ramucirumab (AFP ≥400 ng/mL), nivo + ipi, or durvalumab; atezo + bev or durva + treme may be considered for patients who did not have access to these therapies in the first-line setting, and do not have contraindications. Pembrolizumab or nivolumab are also options for appropriate patients following sorafenib or lenvatinib. Third-line therapy may be considered in Child-Pugh class A patients with good PS, using one of the agents listed previously that has a nonidentical mechanism of action with previously received therapy. A cautious approach to systemic therapy is recommended for patients with Child-Pugh class B advanced HCC. Further guidance on choosing between options is included within the guideline.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Systemic Therapy for Tumor Control in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline.

PURPOSE: To develop recommendations for systemic therapy for well-differentiated grade 1 (G1) to grade 3 (G3) metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS: Eight randomized controlled trials met the inclusion criteria for the systematic review. RECOMMENDATIONS: Somatostatin analogs (SSAs) are recommended as first-line systemic therapy for most patients with G1-grade 2 (G2) metastatic well-differentiated GI-NETs. Observation is an option for patients with low-volume or slow-growing disease without symptoms. After progression on SSAs, peptide receptor radionuclide therapy (PRRT) is recommended as systematic therapy for patients with somatostatin receptor (SSTR)-positive tumors. Everolimus is an alternative second-line therapy, particularly in nonfunctioning NETs and patients with SSTR-negative tumors. SSAs are standard first-line therapy for SSTR-positive pancreatic (pan)NETs. Rarely, observation may be appropriate for asymptomatic patients until progression. Second-line systemic options for panNETs include PRRT (for SSTR-positive tumors), cytotoxic chemotherapy, everolimus, or sunitinib. For SSTR-negative tumors, first-line therapy options are chemotherapy, everolimus, or sunitinib. There are insufficient data to recommend particular sequencing of therapies. Patients with G1-G2 high-volume disease, relatively high Ki-67 index, and/or symptoms related to tumor growth may benefit from early cytotoxic chemotherapy. For G3 GEP-NETs, systemic options for G1-G2 may be considered, although cytotoxic chemotherapy is likely the most effective option for patients with tumor-related symptoms, and SSAs are relatively ineffective. Qualifying statements are provided to assist with treatment choice. Multidisciplinary team management is recommended, along with shared decision making with patients, incorporating their values and preferences, potential benefits and harms, and other characteristics and circumstances, such as comorbidities, performance status, geographic location, and access to care.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline.

PURPOSE: To develop recommendations involving targeted therapies for patients with advanced gastroesophageal cancer. METHODS: The American Society of Clinical Oncology convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS: Eighteen randomized controlled trials met the inclusion criteria for the systematic review. RECOMMENDATIONS: For human epidermal growth factor receptor 2 (HER2)-negative patients with gastric adenocarcinoma (AC) and programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 5, first-line therapy with nivolumab and chemotherapy (CT) is recommended. For HER2-negative patients with esophageal or gastroesophageal junction (GEJ) AC and PD-L1 CPS ≥ 5, first-line therapy with nivolumab and CT is recommended. First-line therapy with pembrolizumab and CT is recommended for HER2-negative patients with esophageal or GEJ AC and PD-L1 CPS ≥ 10. For patients with esophageal squamous cell carcinoma and PD-L1 tumor proportion score ≥ 1%, nivolumab plus CT, or nivolumab plus ipilimumab is recommended; for patients with esophageal squamous cell carcinoma and PD-L1 CPS ≥ 10, pembrolizumab plus CT is recommended. For patients with HER2-positive gastric or GEJ previously untreated, unresectable or metastatic AC, trastuzumab plus pembrolizumab is recommended, in combination with CT. For patients with advanced gastroesophageal or GEJ AC whose disease has progressed after first-line therapy, ramucirumab plus paclitaxel is recommended. For HER2-positive patients with gastric or GEJ AC who have progressed after first-line therapy, trastuzumab deruxtecan is recommended. In all cases, participation in a clinical trial is recommended as it is the panel's expectation that targeted treatment options for gastroesophageal cancer will continue to evolve.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Treatment of Metastatic Colorectal Cancer: ASCO Guideline.

PURPOSE: To develop recommendations for treatment of patients with metastatic colorectal cancer (mCRC). METHODS: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS: Five systematic reviews and 10 randomized controlled trials met the systematic review inclusion criteria. RECOMMENDATIONS: Doublet chemotherapy should be offered, or triplet therapy may be offered to patients with previously untreated, initially unresectable mCRC, on the basis of included studies of chemotherapy in combination with anti-vascular endothelial growth factor antibodies. In the first-line setting, pembrolizumab is recommended for patients with mCRC and microsatellite instability-high or deficient mismatch repair tumors; chemotherapy and anti-epidermal growth factor receptor therapy is recommended for microsatellite stable or proficient mismatch repair left-sided treatment-naive RAS wild-type mCRC; chemotherapy and anti-vascular endothelial growth factor therapy is recommended for microsatellite stable or proficient mismatch repair RAS wild-type right-sided mCRC. Encorafenib plus cetuximab is recommended for patients with previously treated BRAF V600E-mutant mCRC that has progressed after at least one previous line of therapy. Cytoreductive surgery plus systemic chemotherapy may be recommended for selected patients with colorectal peritoneal metastases; however, the addition of hyperthermic intraperitoneal chemotherapy is not recommended. Stereotactic body radiation therapy may be recommended following systemic therapy for patients with oligometastases of the liver who are not considered candidates for resection. Selective internal radiation therapy is not routinely recommended for patients with unilobar or bilobar metastases of the liver. Perioperative chemotherapy or surgery alone should be offered to patients with mCRC who are candidates for potentially curative resection of liver metastases. Multidisciplinary team management and shared decision making are recommended. Qualifying statements with further details related to implementation of guideline recommendations are also included.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update.

PURPOSE: To develop recommendations for adjuvant therapy for patients with resected stage II colon cancer. METHODS: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS: Twenty-one observational studies and six randomized controlled trials met the systematic review inclusion criteria. RECOMMENDATIONS: Adjuvant chemotherapy (ACT) is not routinely recommended for patients with stage II colon cancer who are not in a high-risk subgroup. Patients with T4 tumors are at higher risk of recurrence and should be offered ACT, whereas patients with other high-risk factors, including sampling of fewer than 12 lymph nodes in the surgical specimen, perineural or lymphovascular invasion, poorly or undifferentiated tumor grade, intestinal obstruction, tumor perforation, or grade BD3 tumor budding, may be offered ACT. The addition of oxaliplatin to fluoropyrimidine-based ACT is not routinely recommended, but may be offered as a result of shared decision making. Patients with mismatch repair deficiency/microsatellite instability tumors should not be routinely offered ACT; if the combination of mismatch repair deficiency/microsatellite instability and high-risk factors results in a decision to offer ACT, oxaliplatin-containing chemotherapy is recommended. Duration of oxaliplatin-containing chemotherapy is also addressed, with recommendations for 3 or 6 months of treatment with capecitabine and oxaliplatin or fluorouracil, leucovorin, and oxaliplatin, with decision making informed by key evidence of 5-year disease-free survival in each treatment subgroup and the rate of adverse events, including peripheral neuropathy.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Immunotherapy in Patients With Locally Advanced Esophageal Carcinoma: ASCO Treatment of Locally Advanced Esophageal Carcinoma Guideline Rapid Recommendation Update.

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options.

Oncology Medical Home: ASCO and COA Standards.

PURPOSE: To provide Standards on the basis of evidence and expert consensus for a pilot of the Oncology Medical Home (OMH) certification program. The OMH model is a system of care delivery that features coordinated, efficient, accessible, and evidence-based care and includes a process for measurement of outcomes to facilitate continuous quality improvement. The OMH pilot is intended to inform further refinement of Standards for OMH model implementation. METHODS: An Expert Panel was formed, and a systematic review of the literature on the topics of OMH, clinical pathways, and survivorship care plans was performed using PubMed and Google Scholar. Using this evidence base and an informal consensus process, the Expert Panel developed a set of OMH Standards. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: Three comparative peer-reviewed studies of OMH met the inclusion criteria. In addition, the results from 16 studies of clinical pathways and one systematic review of survivorship care plans informed the evidence review. Limitations of the evidence base included the small number of studies of OMH and lack of longer-term outcomes data. More data were available to inform the specific Standards for pathways and survivorship care; however, outcomes were mixed for the latter intervention. The Expert Panel concluded that in the future, practices should be encouraged to publish the results of OMH interventions in peer-reviewed journals to improve the evidence base. STANDARDS: Standards are provided for OMH in the areas of patient engagement, availability and access to care, evidence-based medicine, equitable and comprehensive team-based care, quality improvement, goals of care, palliative and end-of-life care discussions, and chemotherapy safety. Additional information, including a Standards implementation manual, is available at www.asco.org/standards.

Telehealth in Oncology: ASCO Standards and Practice Recommendations.

PURPOSE: To provide standards and practice recommendations specific to telehealth in oncology. METHODS: A systematic review of the literature on telehealth in oncology was performed, including the use of technologies and telecommunications systems, and other electronic methods of care delivery and sharing of information with patients. The evidence base was combined with the opinion of the ASCO Telehealth Expert Panel to develop telehealth standards and guidance. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: The Expert Panel determined that general guidance on implementing telehealth across general and specialty settings has been published previously and these resources are endorsed. A systematic search for studies on topics specific to oncology resulted in the inclusion of two clinical practice guidelines, 12 systematic reviews, and six primary studies. STANDARDS AND GUIDANCE: Standards and guidance are provided for which patients in oncology can be seen via telehealth, establishment of the doctor-physician relationship, role of allied health professionals, role of advanced practice providers, multidisciplinary cancer conferences, and teletrials in oncology. Additional information is available at www.asco.org/standards.

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline.

PURPOSE: To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to conduct a systematic review of published phase III randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and provide recommended care options for this patient population. RESULTS: Nine phase III randomized controlled trials met the inclusion criteria. RECOMMENDATIONS: Atezolizumab + bevacizumab (atezo + bev) may be offered as first-line treatment of most patients with advanced HCC, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1, and following management of esophageal varices, when present, according to institutional guidelines. Where there are contraindications to atezolizumab and/or bevacizumab, tyrosine kinase inhibitors sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC, Child-Pugh class A liver disease, and ECOG PS 0-1. Following first-line treatment with atezo + bev, and until better data are available, second-line therapy with a tyrosine kinase inhibitor may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with α-fetoprotein ≥ 400 ng/mL), or atezo + bev where patients did not have access to this option as first-line therapy. Pembrolizumab or nivolumab are also reasonable options for appropriate patients following sorafenib or lenvatinib. Consideration of nivolumab + ipilimumab as an option for second-line therapy and third-line therapy is discussed. Further guidance on choosing between therapy options is included within the guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Metastatic Pancreatic Cancer: ASCO Guideline Update.

PURPOSE: The aim of this work was to provide an update to the ASCO guideline on metastatic pancreatic cancer pertaining to recommendations for therapy options after first-line treatment. METHODS: ASCO convened an Expert Panel and conducted a systematic review to update guideline recommendations for second-line therapy for metastatic pancreatic cancer. RESULTS: One randomized controlled trial of olaparib versus placebo, one report on phase I and II studies of larotrectinib, and one report on phase I and II studies of entrectinib met the inclusion criteria and inform the guideline update. RECOMMENDATIONS: New or updated recommendations for germline and somatic testing for microsatellite instability high/mismatch repair deficiency, BRCA mutations, and TRK alterations are provided for all treatment-eligible patients to select patients for recommended therapies, including pembrolizumab, olaparib, larotrectinib, or entrectinib, or potential clinical trials. The Expert Panel continues to endorse the remaining recommendations for second-line chemotherapy, as well as other recommendations related to treatment, follow-up, and palliative care from the 2018 version of this guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Treatment of Locally Advanced Esophageal Carcinoma: ASCO Guideline.

PURPOSE: To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with locally advanced esophageal cancer. METHODS: ASCO convened an Expert Panel to conduct a systematic review of the more recently published literature (1999-2019) on therapy options for patients with locally advanced esophageal cancer and provide recommended care options for this patient population. RESULTS: Seventeen randomized controlled trials met the inclusion criteria. Where possible, data were extracted separately for squamous cell carcinoma and adenocarcinoma. RECOMMENDATIONS: Multimodality therapy for patients with locally advanced esophageal carcinoma is recommended. For the subgroup of patients with adenocarcinoma, preoperative chemoradiotherapy or perioperative chemotherapy should be offered. For the subgroup of patients with squamous cell carcinoma, preoperative chemoradiotherapy or chemoradiotherapy without surgery should be offered. Additional subgroup considerations are provided to assist with implementation of these recommendations. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Patient-Centered Standards for Medically Integrated Dispensing: ASCO/NCODA Standards.

PURPOSE: To provide standards for medically integrated dispensing of oral anticancer drugs and supportive care medications. METHODS: An Expert Panel was formed, and a systematic review of the literature on patient-centered best practices for the delivery of oral anticancer and supportive care drugs was performed to April 2019 using PubMed and Google Scholar. Available patient-centered standards, including one previously developed by the National Community Oncology Dispensing Association (NCODA), were considered for endorsement. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: A high-quality systematic review that was current to May 2016 was adopted into the evidence base. Five additional primary studies of multifaceted interventions met the inclusion criteria. These studies generally included a multicomponent intervention, often led by an oncology pharmacist, and also included patient education and regular follow-up and monitoring. These interventions resulted in significant improvements to patient quality and safety and demonstrated improvements in adherence and other patient outcomes. CONCLUSION: The findings of the systematic review were consistent with the NCODA patient-centered standards for patient relationships and education, adherence, safety, collection of data, documentation, and other areas. NCODA standards were adopted and used as basis for these American Society of Clinical Oncology/NCODA standards. Additional information is available at www.asco.org/mid-standards.

Is younger better? Donor age less than 25 does not predict more favorable outcomes after in vitro fertilization.

OBJECTIVE: To determine whether younger oocyte donor age is associated with better outcomes after in vitro fertilization (IVF) compared with older oocyte donor age. DESIGN: A retrospective cohort study. SETTING: Large academically affiliated infertility treatment center. PATIENTS: We included all women ≥ 18 years who started their first fresh cycle using donor oocytes at our center from January 2002 through October 2017; only the first oocyte recipient cycle was analyzed. INTERVENTION: Log-binomial regression was used to compare the incidence of clinical pregnancy and live birth among the following donor age groups: < 25 years, 25 to < 30 years, and 30 to <35 years. MAIN OUTCOME MEASURE: Incidence of clinical pregnancy and live birth among donor age groups. RESULTS: We included 774 donor cycles; 269 (34.8%) used donors < 25 years, 399 (51.6%) used donors 25 to < 30 years, and 106 (13.7%) used donors 30 to < 35 years. Median donor age was 26 years (range 18-34.5), and median recipient age and partner age were both 42 years. Per cycle start, after adjusting for recipient age, cycles using donors < 25 years were not associated with a higher incidence of clinical pregnancy (RR 0.90; 95% CI 0.77-1.06) or live birth (RR 0.87; 95% CI 0.72-1.04) compared with donors age 25-< 30 years. CONCLUSIONS: Donor age < 25 was not associated with better outcomes after IVF. Under the age of 30, the prioritization of <25 year old donors may not be recommended given the lack of evidence for superior pregnancy or live birth outcomes.

Duration of Oxaliplatin-Containing Adjuvant Therapy for Stage III Colon Cancer: ASCO Clinical Practice Guideline.

PURPOSE: To develop recommendations for duration of adjuvant chemotherapy with a fluoropyrimidine and oxaliplatin for patients with completely resected stage III colon cancer based on the results of trials of 3 months compared with 6 months of treatment. METHODS: ASCO convened an Expert Panel and conducted a systematic review of relevant studies. The guideline recommendations were based on the review of evidence by the Expert Panel. RESULTS: Pooled data from the six International Duration Evaluation of Adjuvant Chemotherapy (IDEA) Collaboration randomized controlled trials comprise the evidence base for these guideline recommendations. RECOMMENDATIONS: The recommendations for therapy duration apply to patients with completely resected stage III colon cancer who are being offered adjuvant chemotherapy with oxaliplatin and a fluoropyrimidine. Recommendations are informed by the findings of a recent pooled analysis of clinical trials that compared 6 months versus 3 months of oxaliplatin-based chemotherapy. For patients at a high risk of recurrence (T4 and/or N2), adjuvant chemotherapy should be offered for a duration of 6 months. For patients at a low risk of recurrence (T1, T2, or T3 and N1), either 6 months of adjuvant chemotherapy or a shorter duration of 3 months may be offered on the basis of a potential reduction in adverse events and no significant difference in disease-free survival with the 3-month regimen. In determining duration of therapy, the Expert Panel recommends a shared decision-making approach, taking into account patient characteristics, values and preferences, and other factors and including a discussion of the potential for benefit and risks of harm associated with treatment duration. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Adjuvant Therapy for Resected Biliary Tract Cancer: ASCO Clinical Practice Guideline.

PURPOSE: To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with resected biliary tract cancer. METHODS: ASCO convened an Expert Panel to conduct a systematic review of the literature on adjuvant therapy for resected biliary tract cancer and provide recommended care options for this patient population. RESULTS: Three phase III randomized controlled trials, one phase II trial, and 16 retrospective studies met the inclusion criteria. RECOMMENDATIONS: Based on evidence from a phase III randomized controlled trial, patients with resected biliary tract cancer should be offered adjuvant capecitabine chemotherapy for a duration of 6 months. The dosing used in this trial is described in the qualifying statements, while it should be noted that the dose of capecitabine may also be determined by institutional and regional practices. Patients with extrahepatic cholangiocarcinoma or gallbladder cancer and a microscopically positive surgical resection margin (R1 resection) may be offered chemoradiation therapy. A shared decision-making approach is recommended, considering the risk of harm and potential for benefit associated with radiation therapy for patients with extrahepatic cholangiocarcinoma or gallbladder cancer. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .