Four full panel meetings were held, and members were asked to provide ongoing input on the quality and assessment of the evidence, generation of recommendations, and draft content and to review and approve drafts during the entire guideline development. ASCO staff met routinely with the Expert Panel co-chairs and corresponded with the panel via email to coordinate the process to completion. The guideline recommendations were sent for an open-comment period of 2 weeks allowing the public to review and comment on the recommendations after submitting a confidentiality agreement. Public comments were taken into consideration while finalizing the recommendations. Members of the Expert Panel were responsible for reviewing and approving the penultimate version of the guideline, which was then circulated for external review and submitted to the Journal of Clinical Oncology for editorial review and consideration for publication. All ASCO guidelines are ultimately reviewed and approved by the Expert Panel and the ASCO Evidence Based Medicine Committee before publication. All funding for the administration of the project was provided by ASCO.Articles were excluded from the systematic review if they were meeting abstracts not subsequently published in peer-reviewed journals; editorials, commentaries, letters, news articles, case reports, cannabis growing equipment narrative reviews; or published in a language other than English. A guideline implementability review was conducted.
On the basis of the review, revisions were made to the draft to clarify recommended actions for clinical practice. Ratings for the type and strength of the recommendation and evidence quality are provided with each recommendation. The quality of the evidence for each outcome was assessed using the Cochrane Risk of Bias tool and elements of the GRADE quality assessment and recommendations development process. GRADE quality assessment labels were assigned for each outcome by the project methodologist in collaboration with the Expert Panel co-chairs and reviewed by the full Expert Panel. When little or no direct evidence was available, the Expert Panel considered the appropriateness of providing good practice statements on the basis of discussion and criteria provided by the GRADE Working Group. Good practice statements are recommendations that are important and actionable but not appropriate for formal ratings of the quality of the evidence. The ASCO Expert Panel and guidelines staff will work with co-chairs and Expert Panel to update these guidelines with any substantive changes as evidence emerges. On the basis of a formal review of the emerging literature, ASCO will determine the need to update. The ASCO Guidelines Methodology Manual provides additional information about the guideline update process. This manual is the most recent information as of the publication date.
The Clinical Practice Guidelines and other guidance published herein are provided by ASCO to assist providers in clinical decision-making. The information herein should not be relied upon as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge between the time information is developed and when it is published or read. The information is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This information does not mandate any particular course of medical care. Further, the information is not intended to substitute for the independent professional judgment of the treating provider, as the information does not account for individual variation among patients. Recommendations specify the level of confidence that the recommendation reflects the net effect of a given course of action. The use of words like “must,” “must not,” “should,” and “should not” indicate that a course of action is recommended or not recommended for either most or many patients, but there is latitude for the treating physician to select other courses of action in individual cases. In all cases, the selected course of action should be considered by the treating provider in the context of treating the individual patient. Use of the information is voluntary.
ASCO does not endorse third-party drugs, devices, services, or therapies used to diagnose, treat, monitor, manage, or alleviate health conditions. Any use of a brand or trade name is for identification purposes only. ASCO provides this information on an “as is” basis and makes no warranty, express or implied, regarding the information. ASCO specifically disclaims any warranties of merchantability or fitness for a particular use or purpose. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of this information, or for any errors or omissions.The Expert Panel was assembled in accordance with ASCO’s Conflict of Interest Policy Implementation for Clinical Practice Guidelines . All members of the Expert Panel completed ASCO’s disclosure form, which requires disclosure of financial and other interests, including relationships with commercial entities that are reasonably likely to experience direct regulatory or commercial impact as a result of promulgation of the guideline. Categories for disclosure include employment; leadership; stock or other ownership; honoraria, consulting or advisoryrole; speaker’s bureau; research funding; patents, royalties, other intellectual property; expert testimony; travel, accommodations, expenses; and other relationships. In accordance with the Policy, the majority of the members of the Expert Panel did not disclose any relationships constituting a conflict under the Policy.A total of 366 publications were identified in the literature search. After applying the eligibility criteria, 16 remained: 11 systematic reviews and five RCTs or cohort studies not captured by the included systematic reviews. After the completion of the literature search, the Multinational Association for Supportive Care in Cancer published two additional cannabis systematic reviews, one on psychological symptoms and one on cancer pain. These publications were added to the current review. In RCTs of cannabis and/or cannabinoids concerning treatment toxicity or symptom management in oncology, the primary outcomes of interest have been chemotherapy-induced nausea and vomiting ; cachexia, poor appetite, and weight loss; and pain. Studies have also reported on sleep, QOL, and mood outcomes. Limitations of this body of evidence include varying interventions, lack of standardized universal good manufacturing practices, small sample sizes, short follow-up, and limited information regarding effectiveness in the setting of current supportive care practices. Few studies have addressed antineoplastic effects in adults with cancer, including potential interactions with various systemic cancer therapies.
Nevertheless, one emerging question is whether cannabis negatively affects outcomes in adults with cancer receiving immunotherapy. Characteristics and results of included studies are provided in the Data Supplement .The quality of evidence was assessed for each outcome of interest. This rating includes factors such as study design, consistency of results, directness of evidence, precision, publication bias, and magnitude of effect, assessed by one reviewer. Evidence quality ratings for cannabis and/or cannabinoids in relation to cancer symptoms, treatment toxicity, and QOL are provided in Table 2, with additional tables and details provided in the Data Supplement. Refer to Appendix Table A1 for definitions of the quality of the evidence and the Methodology Manual for more information. For cannabinoids other than the US Food and Drug Administration – approved products, evidence was very low or low for all outcomes.Translating these guidelines into clinical practice calls for the recognition of key points. To mitigate both undue task burden on ground-level clinicians and variability in clinical practice, recommendation 1.1 calls on health systems to participate in the provision of unbiased, evidence-based cannabis and/or cannabinoid educational resources and to systematically disseminate them to all in patient-facing roles. Such system level action empowers members of multidisciplinary oncology clinical teams broadly to guide adults with cancer to cannabis and/or cannabinoid educational resources deemed appropriate by their organization. Recommendations 1.2 and 1.3 also encourage clinicians to explore the role of cannabis and/or cannabinoids for symptom management, cannabis drying trays proactively or in response to patient or caregiver requests. When faced with a dearth of effective options with higher levels of evidence, consideration of cannabis and/or cannabinoids for symptom relief—specifically for refractory CINV when standard-of-care antiemetic regimens are ineffective—now falls within accepted standards of oncologic practice. Evidence regarding antineoplastic effects of cannabis and/or cannabinoids is limited. A phase Ib RCT of 21 individuals with recurrent glioblastoma after radiotherapy and first-line chemotherapy with temozolomide reported that the addition of nabiximols to dose-intense temozolomide had acceptable safety and tolerability. The study did not identify any drug-drug interactions. Owing to the high interpatient variability in pharmacokinetics and pharmacodynamics of nabiximols, dosing was individualized to 3–12 sprays/day, on the basis of a dose-ranging trial in adults with chronic pain. Investigators also explored an efficacy end point of 6-month progression-free survival and 1-year overall survival . Although PFS at 6 months was the same, 1-year survival was higher in the nabiximols arm than in the placebo arm. Of note, the small study was not powered for survival as an end point. The investigators recommended further exploration in an adequately powered RCT. The possibility that cannabis and/or cannabinoids may worsen outcomes among adults with cancer treated with immunotherapy has been reported by two cohort studies. In a prospective observational study of 102 consecutive adults with advanced cancer treated with immunotherapy , use of cannabis was associated with a shorter median time to progression and shorter median OS . Additionally, in a retrospective study of 140 adults with advanced cancer treated with nivolumab, cannabis use was not significantly associated with PFS or OS but was associated with a lower treatment response rate . Given the study design limitations, these data are hypothesis-generating, requiring further validation. A 2023 MASCC guideline nonetheless recommended against cannabinoids for any indication among adults with cancer receiving a checkpoint inhibitor. Clinical interpretation.: Discordance between the Expert Panel’s recommendation against cannabis and/or cannabinoids as an anticancer treatment and the plethora of anecdotes supporting their use warrants discussion. Online information about cannabis and/or cannabinoids as cancer cures is widespread, if often misaligned with scientific evidence. Such misinformation can spur unrealistic expectations for cancer treatment that is natural and free from side effects. Indeed, online searches for cannabis and cancer have increased 10 times the rate of searches for standard therapies, with cannabis as a cancer cure representing the largest category of searches on alternative cancer treatments. In a recent review, the top false news story claiming cannabis and/or cannabinoids as a cancer cure generated over 100-fold more social media engagements than the top evidence-based accurate news article debunking the story. This trend is not limited to the online space.In a review of 77 unique case reports describing adults with various cancers using cannabis and/or cannabinoids as a cancer-directed treatment, the supporting evidence was judged to be weak in more than 80% of cases. Unfortunately, a published series of adults with cancer receiving cannabis and/or cannabinoids excluded those receiving <6 months of treatment while disregarding the concomitant conventional anticancer treatment in nearly all patients. This perhaps well-intentioned but uncritical approach to reporting data was perpetuated in a recent review, which used a social media report as evidence of continuing cannabis and/or cannabinoid benefit. These problems reinforce the need for high-quality evidence to support clinical interventions before incorporating cannabis and/or cannabis as anticancer agents.A specific issue pertains to combining cannabis and cannabinoids with anticancer immunotherapies. Immunotherapies are established treatment strategies to activate the immune system to recognize and attack cancer cells. Immunotherapies changed the outcome of many cancers and even provided potential cures in metastatic disease. Nevertheless, efficacy is often limited because of local tumor-induced immune suppression. While broadly, cannabis and/or cannabinoids have anti-inflammatory properties, which may be beneficial in reducing cancer-associated inflammation, such properties are likely strongly undesirable during targeted activation of T-cell–specific anticancer immunotherapy. Cannabinoids modulate various aspects of the immune system: the proliferation, activation, and cytotoxic activity of T cells; the production of cytokines and chemokines by granulocytes; the function of dendritic and natural killer cells; the chemotactic capacity of neutrophils; and/or the rapid expansion and recruitment of immunosuppressive immature myeloid cells and myeloid-derived suppressor cells. Although the interaction between cannabinoids and anticancer immunotherapy is likely complex and incompletely understood, recent studies provide clinically relevant observations. For example, cannabis consumption was associated with reduced response rates to nivolumab. In a prospective follow-up study of adults with various metastatic cancers initiating immunotherapy, cannabis consumption correlated with a significant decrease in time to tumor progression and decreased OS.