Head and neck cancer is a broad family of diseases, most of which are of squamous cell origin, affecting the epithelial mucosa lining the upper aerodigestive tract. They often recur or are ...progressive despite multimodality treatment approaches, resulting in a poor prognosis. Given the progressive aging of the global population, the probability to plan an active and eventually toxic treatment for an older patient, with either curative or palliative intent, can no longer be considered as an uncommon occurrence. A crucial point in offering a systemic treatment to older patients with head and neck squamous cell carcinoma is that they are underrepresented in randomised clinical trials, and evidence-based guidelines are lacking, while, from a clinical point of view, these patients may have varying grades of resilience to anticancer treatments due to differences in their health, social and/or economic status. Our aim is to draw attention to the older patient population suffering from recurrent and/or metastatic head and neck squamous cell carcinoma and to address some open questions, such as possible differences in epidemiology and biology compared with their younger counterparts; to highlight frailty and its components by discussing how to measure and use it to personalise treatment; to evaluate which outcomes should be best achieved in the older adult setting; finally, in the era of immunotherapy, to examine whether there are differences to be addressed when considering new treatments for older patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Transparent and precise endpoint definitions are a crucial aspect of clinical trial conduct and reporting, and are used to communicate the benefit of an intervention. Previous studies have identified ...inconsistencies in endpoint definitions across oncological clinical trials. Here, the Head and Neck Cancer International Group assessed endpoint definitions from phase 3 trials or trials considered practice-changing for patients with recurrent or metastatic mucosal head and neck squamous cell carcinoma, published between 2008 and 2021. We identify considerable and global heterogeneity in endpoint definitions, which undermines the interpretation of results and development of future studies. We show how fundamental components of even incontrovertible endpoints such as overall survival vary widely, highlighting an urgent need for increased rigour in reporting and harmonisation of endpoints.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The emergence of the precision medicine paradigm in oncology has led to increasing interest in the integration of real-world data (RWD) into cancer clinical research. As sources of real-world ...evidence (RWE), such data could potentially help address the uncertainties that surround the adoption of novel anticancer therapies into the clinic following their investigation in clinical trials. At present, RWE-generating studies which investigate antitumour interventions seem to primarily focus on collecting and analysing observational RWD, typically forgoing the use of randomisation despite its methodological benefits. This is appropriate in situations where randomised controlled trials (RCTs) are not feasible and non-randomised RWD analyses can offer valuable insights. Nevertheless, depending on how they are designed, RCTs have the potential to produce strong and actionable RWE themselves. The choice of which methodology to employ for RWD studies should be guided by the nature of the research question they are intended to answer. Here, we attempt to define some of the questions that do not necessarily require the conduct of RCTs. Moreover, we outline the strategy of the European Organisation for Research and Treatment of Cancer (EORTC) to contribute to the generation of robust and high-quality RWE by prioritising the execution of pragmatic trials and studies set up according to the trials-within-cohorts approach. If treatment allocation cannot be left up to random chance due to practical or ethical concerns, the EORTC will consider undertaking observational RWD research based on the target trial principle. New EORTC-sponsored RCTs may also feature concurrent prospective cohorts composed of off-trial patients.
•The role of real-world data (RWD) in cancer clinical research is increasing.•A false dichotomy exists between RWD studies and randomised controlled trials (RCTs).•There are different methodologies for RWD studies, including RCT designs.•The methodology to be employed should be determined by the research question.•We outline the RWD strategy of a large academic clinical cancer research organisation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Universally agreed criteria for cisplatin ineligibility in LA SCCHN are needed.•Cisplatin-ineligible patients have limited adjuvant setting treatment options.•Radiotherapy alone is an evidence-based ...option for cisplatin-ineligible patients.•Randomized phase 3 trials of cisplatin-sparing regimens are urgently needed.
For the past 2 decades, cisplatin-based adjuvant chemoradiotherapy (CRT) has remained the standard of care for patients with resected, locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) who are at high risk of disease recurrence. However, many patients are deemed ineligible for cisplatin-based CRT because of poor performance status, advanced biological age, poor renal function, or hearing loss. Because outcomes with radiotherapy (RT) alone remain poor, patients at high risk of disease recurrence deemed ineligible to receive cisplatin are a population with a significant unmet medical need, and alternative systemic therapy options in combination with RT are urgently needed. Clinical guidelines and consensus documents have provided definitions for cisplatin ineligibility; however, areas of debate include thresholds for age and renal impairment and criteria for hearing loss. Furthermore, the proportion of patients with resected LA SCCHN who are cisplatin ineligible remains unclear. Because of a scarcity of clinical studies, treatment selection for patients with resected, high-risk LA SCCHN who are deemed ineligible to receive cisplatin is often based on clinical judgment, with few treatment options specified in international guidelines. In this review, we discuss considerations related to cisplatin ineligibility in patients with LA SCCHN, summarize the limited clinical evidence for adjuvant treatment of patients with resected high-risk disease, and highlight ongoing clinical trials that have the potential to provide new treatment options in this setting.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Nonsurgical treatment in advanced head & neck cancer has still unsatisfactory results.•Altered fractionation chemoradiotherapy has been used as an intensification strategy.•We compared concurrent ...three-/four-weekly high-dose versus weekly low-dose cisplatin.•In this respect, high-dose single-agent cisplatin is superior to low-dose infusions.
Altered fractionation radiotherapy and concomitant chemoradiotherapy represent commonly used intensification strategies in the management of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). This meta-analysis compares compliance, safety, and efficacy between two single-agent cisplatin schedules given concurrently with altered fractionation radiotherapy.
We systematically searched for prospective trials of patients with LA-SCCHN who received post-operative or definitive altered fractionation concurrent chemoradiotherapy. High-dose cisplatin once every three to four weeks (100 mg/m2, 2 doses) was compared with a weekly low-dose protocol (≤50 mg/m2, ≥4 doses). The primary outcome was overall survival. The secondary endpoints comprised treatment adherence, acute and late toxicities, and objective response rate.
Twelve studies with 1373 patients treated with definitive chemoradiotherapy were included. Compared to the weekly low-dose cisplatin regimen, the three- to four-weekly high-dose cisplatin regimen improved overall survival (p=.0185), was more compliant with respect to receiving all planned cycles of cisplatin (71% versus 95%, p=.0353), and demonstrated less complications in terms of severe (grade 3—4) acute mucositis and/or stomatitis (75% versus 40%, p=.0202) and constipation (8% versus 1%, p=.0066), toxic deaths (4%, versus 1%, p=.0168), 30-day mortality (8% versus 3%, p=.0154), and severe late subcutaneous fibrosis (21% versus 2%, p<.0001). Overall and complete response rates were similar between both chemotherapy schedules.
In chemoradiotherapy incorporating altered fractionation, two cycles of high-dose cisplatin with a three to four week interval are superior to weekly low-dose schedules. Further studies should identify those who might derive the greatest benefit from this intensified approach.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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