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Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 3  |  Page : 580-582

Does chemoradiotherapy benefit older patients with squamous cell carcinomas of the head-and-neck?

1 Department of Medical Oncology, Mazumdar Shaw Cancer Center, Bengaluru, Karnataka, India
2 Department of Medical Oncology, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India

Date of Submission04-Aug-2020
Date of Decision05-Aug-2020
Date of Acceptance06-Aug-2020
Date of Web Publication19-Sep-2020

Correspondence Address:
Keechilat Pavithran
Department of Medical Oncology, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham, P.O. AIMS Ponekkara, Kochi - 682 041, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CRST.CRST_267_20

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How to cite this article:
Srinivasalu VK, Pavithran K. Does chemoradiotherapy benefit older patients with squamous cell carcinomas of the head-and-neck?. Cancer Res Stat Treat 2020;3:580-2

How to cite this URL:
Srinivasalu VK, Pavithran K. Does chemoradiotherapy benefit older patients with squamous cell carcinomas of the head-and-neck?. Cancer Res Stat Treat [serial online] 2020 [cited 2021 Jul 27];3:580-2. Available from: https://www.crstonline.com/text.asp?2020/3/3/580/295511

As per GLOBOCAN India 2018, squamous cell carcinomas of the head and neck (SCCHN) account for around 16% of the cancer burden in Indian men. Treatment of locally advanced (LA)-SCCHN involves a multidisciplinary approach, with surgical resection being the primary treatment modality followed by adjuvant radiation or chemoradiation (CRT), based on the presence of high-risk features such as positive margins or extracapsular nodal extension; for LA laryngeal or hypopharyngeal cancers, organ-preserving CRT is the standard of care. The guidelines on how to treat older patients with LA-SCCHN are sparse for multiple reasons, including the underrepresentation or exclusion of older patients in the landmark clinical trials,[1],[2] fear of poor tolerance, associated comorbidities, and a meta-analysis proving no benefit along with increased toxicity in patients aged >70 years on treatment with CRT.[3] Like with most cancers, treatment paradigms for older patients with SCCHN are extrapolated from retrospective studies and subgroup analyses or adapted from treatment designs curated for their younger and fitter counterparts. This poses a threat of unacceptable adverse events or undertreatment of the older patients, resulting in compromised long-term survival outcomes and impaired quality of life.[4]

Although the geriatric population comprises a significant proportion of patients with SCCHN, they are usually underrepresented in large clinical trials. As the average age for the diagnosis of smoking-related SCCHN is 60 years, and that for smokeless tobacco-associated SCCHN is 78 years,[5] there is an urgent requirement to identify the optimal treatment regimen for older patients with LA-SCCHN without compromising their longevity. To help refine the standard of care in LA-SCCHN, a prospective randomized study was conducted by Noronha et al.,[6] comparing once-a-week cisplatin to once-in-three-weeks cisplatin along with standard-dose radiation in patients with LA-SCCHN. Singh et al. performed an unplanned post hoc analysis of this prospective study,[7] which primarily aimed to compare the outcomes and toxicities of CRT between older and younger patients with LA-SCCHN. This analysis included patients with oral cavity, laryngeal, and hypopharyngeal primaries.

This prospective study randomized 300 patients in a 1:1 ratio to receive either once-a-week cisplatin or once-in-three-weeks cisplatin in combination with standard-dose radiation. For the post hoc subset analysis based on age, the patients were divided into two groups, namely, younger (aged <60 years) and older (aged 60–70 years). CRT resulted in a statistically significantly better locoregional control (LRC) at 2 years in the older patients (100%) compared to the younger patients (67.1%) (P = 0.018), which was the primary end point of the study. The median progression-free survival and overall survival (OS) were 24.4 months and 41.3 months, respectively, in the younger group and were not reached in the older group after a median follow-up of 22 months. All Grade adverse events reported were similar in both the arms, except for leukopenia (17.6% vs. 8.9%) and neutropenia (17.6% vs. 6.4%), which were more frequent in the older patients. Dysphagia was the most common nonhematological Grade 3 or higher toxicity. There was a need for feeding tube insertion in 64.3% of the older patients while on treatment. Notably, despite similar cisplatin doses and schedules, there was no difference in the adverse events, rates of delay in chemotherapy, rates of hospitalization, or treatment-related mortality between the two arms. However, the dose reduction rates were higher in the older patients (17.6% vs. 8.1%) (P = 0.22).

Based on this post hoc analysis, the authors concluded that both the once-a-week cisplatin and once-in-three-weeks cisplatin protocols were safe and well tolerated in geriatric patients with SCCHN. Due to the unequal distribution of patients in the study (283 younger patients comprising 94.3% of the cohort), these data serve as a case series to generate hypotheses rather than providing definitive evidence of the safety and efficacy of CRT in older patients. It is unclear why only 5.7% of the patients belonged to the older group in this trial; given that the median age at diagnosis for patients with SCCHN is 60 years, it would have been advantageous to illustrate how many older patients were excluded in the trial-screening process and what were the reasons for their exclusion. This will help us to better understand how older patients could be appropriately selected to achieve excellent results. In the absence of this crucial information, it is impossible to extrapolate results from 17 patients to the general population.

Besides a small sample size (of the older patients), another limitation was that none of the geriatric tools was used to assess the comorbidities and other nononcologic vulnerabilities among these patients. Nutritional and functional status are prognostic factors for OS[8] and 1-year mortality[9] in older patients with cancer. Furthermore, patients above the chronological age of 70 years were excluded from the study. Chronological age is not a surrogate marker for the patients' tolerance for chemotherapy or expected response to treatment; hence, a thorough assessment of the life expectancy, performance/functional status, social support, and patient preference, along with a geriatric assessment, should be done before deciding the optimal treatment for any older patient with SCCHN.

In the recently reported JCOG1008 Phase II/III study, 261 patients with SCCHN (with a median age of 62 years) showed noninferiority of once-a-week cisplatin in comparison to once-in-three-weeks cisplatin and radiotherapy (RT) in postoperative high-risk SCCHN; however, a better local relapse-free survival and favorable safety profile were observed with weekly cisplatin and RT.[10] This study suggests that in older, fit patients with LA-SCCHN with good performance status, CRT with cisplatin-based chemotherapy, either once-a-week or once-in-three-weeks, should be considered the preferred treatment of choice.

For geriatric patients who are at a higher risk of acute kidney injury, electrolyte disturbances, or hearing loss induced by high-dose cisplatin, carboplatin can be considered an attractive alternative. The study from the Surveillance, Epidemiology, and End Results Program database comprising 807 patients with LA-SCCHN analyzed the cancer-specific outcomes following cisplatin- versus carboplatin-based RT and found carboplatin-based RT to be equivalent to cisplatin-based therapy but superior to RT alone and RT with concurrent cetuximab.[11] Similarly, a large retrospective study by Beckham et al. compared the efficacy of cisplatin, carboplatin, and cetuximab with RT in human papillomavirus (HPV)-unrelated LA-SCCHN and found carboplatin-based regimens to be a more tolerable alternative for patients with HPV-negative tumors with superior LRC and OS.[12] These studies suggest that carboplatin can be considered an alternative to cisplatin, at least in those patients who are deemed cisplatin ineligible. However, prospective trials are needed to confirm this hypothesis.

The unplanned subset analysis of CRT in the older population by Singh et al.,[7] published in this issue, despite its limitations, is promising; however, we need a well-designed multi-institutional study for older (>60 years) patients with LA-SCCHN to settle this issue. An optimal study design for the future could be a comprehensive geriatric assessment followed by the randomization of patients into three arms – once-a-week cisplatin with RT, once-in-three-weeks cisplatin with RT, and once-a-week carboplatin at area under the curve-2 with RT – with further stratification based on the HPV/p16 status of the oropharyngeal, laryngeal, and hypopharyngeal tumors.

  References Top

Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937-44.  Back to cited text no. 1
Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, et al. An intergroup Phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 2003;21:92-8.  Back to cited text no. 2
Pignon JP, le Maître A, Maillard E, Bourhis J. MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92:4-14.  Back to cited text no. 3
VanderWalde NA, Fleming M, Weiss J, Chera BS. Treatment of older patients with head and neck cancer: A review. Oncologist 2013;18:568-78.  Back to cited text no. 4
Vigneswaran N, Tilashalski K, Rodu B, Cole P. Tobacco use and cancer. A reappraisal. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;80:178-82.  Back to cited text no. 5
Noronha V, Joshi A, Patil VM, Agarwal J, Ghosh-Laskar S, Budrukkar A, et al. Once-a-week versus once-every-3-weeks cisplatin chemoradiation for locally advanced head and neck cancer: A phase III randomized non inferiority trial. J Clin Oncol 2018;36:1064-72.  Back to cited text no. 6
Singh GK, Noronha V, Patil VM, Menon N, Joshi A, Prabhash K. Safety and efficacy of concurrent chemoradiotherapy for head-and-neck cancers in older versus younger patients: Post hoc analysis of a randomized controlled trial. Cancer Res Stat Treat 2020;3:482-8.  Back to cited text no. 7
  [Full text]  
Kenis C, Baitar A, Decoster L, De Grève J, Lobelle JP, Flamaing J, et al. The added value of geriatric screening and assessment for predicting overall survival in older patients with cancer. Cancer 2018;124:3753-63.  Back to cited text no. 8
Deudekom FJ, Velden LA, Zijl WH, Schimberg AS, Langeveld AP, Slingerland M, et al. Geriatric assessment and 1-year mortality in older patients with cancer in the head and neck region: A cohort study. Head Neck 2019;41:2477-83.  Back to cited text no. 9
Kiyota N, Tahara M, Fujii H, Yamazaki T, Mitani H, Iwae S, et al. Phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck (JCOG1008). J Clin Oncol 2020;38 (15 Suppl):6502.  Back to cited text no. 10
Xiang M, Colevas AD, Holsinger FC, Le QX, Beadle BM. Survival after definitive chemoradiotherapy with concurrent cisplatin or carboplatin for head and neck cancer. J Natl Compr Canc Netw 2019;17:1065-73.  Back to cited text no. 11
Beckham TH, Barney C, Healy E, Wolfe AR, Branstetter A, Yaney A, et al. Platinum-based regimens versus cetuximab in definitive chemoradiation for human papillomavirus-unrelated head and neck cancer. Int J Cancer 2020;147:107-15.  Back to cited text no. 12


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