Surrogate endpoints for overall survival in locally advanced head and neck cancer: meta-analyses of individual patient data (original) (raw)
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Altered fractionation and adjuvant chemotherapy for head and neck squamous cell carcinoma
Head & Neck, 2009
Background. The aim of this review was to discuss the role of altered fractionation and adjuvant chemotherapy for patients treated with definitive radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC). Methods. This review explores the pertinent literature and discusses the optimal management of previously untreated patients with stage III-stage IVA and/or-B HNSCCs. Results. Depending on the schedule, altered fractionation improves locoregional control and survival. Both hyperfractionation and concomitant boost RT improve locoregional control and are associated with improved overall survival (OS). Adjuvant chemotherapy improves OS; the greatest impact is observed after concomitant versus induction or maintenance chemotherapy. Monochemotherapy appears to be equivalent to polychemotherapy. Drugs associated with the greatest survival benefit include fluorouracil and cisplatin. Intraarterial chemotherapy offers no advantage over intravenous chemotherapy. Concomitant cetuximab and RT results in improved outcomes similar to those observed after concomitant cisplatin-based chemotherapy and RT. Conclusions. Altered fractionation and/or concomitant chemotherapy result in improved outcomes compared with conventionally fractionated definitive RT alone for stage IIIstage IV HNSCC. The optimal combination of RT fractionation and chemotherapy remains unclear. V
When is chemotherapy in head and neck squamous cell carcinoma not indicated?
European Archives of Oto-Rhino-Laryngology, 2014
associated with treatment. The goals of HNSCC therapy can be categorized as either curative, employing either surgery and/or radiotherapy as a therapeutic backbone, or palliative, where symptom management and maintenance or improvement of quantity and quality of life are the primary focus. Systemic therapies (chemotherapy and targeted molecular therapeutics) have been an important addition to the therapeutic armamentarium against HNSCC. Although generally palliative when employed as a single treatment modality, systemic therapy concurrent with radiation has become an important curative option for patients with advanced locoregional disease as initial therapy or in the high-risk postoperative setting. Randomized clinical trials have demonstrated that systemic therapy concurrent with This paper was written by members of the International Head and Neck Scientific Group (www.IHNSG.com).
2006
Background: Former meta-analyses have shown a survival benefit for the addition of chemotherapy (CHX) to radiotherapy (RT) and to some extent also for the use of hyperfractionated radiation therapy (HFRT) and accelerated radiation therapy (AFRT) in locally advanced squamous cell carcinoma (SCC) of the head and neck. However, the publication of new studies and the fact that many older studies that were included in these former meta-analyses used obsolete radiation doses, CHX schedules or study designs prompted us to carry out a new analysis using strict inclusion criteria. Methods: Randomised trials testing curatively intended RT (≥60 Gy in >4 weeks/>50 Gy in <4 weeks) on SCC of the oral cavity, oropharynx, hypopharynx, and larynx published as full paper or in abstract form between 1975 and 2003 were eligible. Trials comparing RT alone with concurrent or alternating chemoradiation (5-fluorouracil (5-FU), cisplatin, carboplatin, mitomycin C) were analyzed according to the employed radiation schedule and the used CHX regimen. Studies comparing conventionally fractionated radiotherapy (CFRT) with either HFRT or AFRT without CHX were separately examined. End point of the meta-analysis was overall survival. Results: Thirty-two trials with a total of 10 225 patients were included into the meta-analysis. An overall survival benefit of 12.0 months was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p < 0.001). Separate analyses by cytostatic drug indicate a prolongation of survival of 24.0 months, 16.8 months, 6.7 months, and 4.0 months, respectively, for the simultaneous administration of 5-FU, cisplatin-based, carboplatin-based, and mitomycin C-based CHX to RT (each p < 0.01). Whereas no significant gain in overall survival was observed for AFRT in comparison to CFRT, a substantial prolongation of median survival (14.2 months, p < 0.001) was seen for HFRT compared to CFRT (both without CHX). Conclusion: RT combined with simultaneous 5-FU, cisplatin, carboplatin, and mitomycin C as single drug or combinations of 5-FU with one of the other drugs results in a large survival advantage irrespective the employed radiation schedule. If radiation therapy is used as single modality, hyperfractionation leads to a significant improvement of overall survival. Accelerated radiation therapy alone, especially when given as split course radiation schedule or extremely accelerated treatments with decreased total dose, does not increase overall survival.
IRA - international journal of applied sciences, 2016
Locally advanced Head and neck cancers (LAHNSCCs) are emerging as an important public health issue in India. Our study was designed to provide NACT to LAHNSCC patients followed by comparison between chemoradiation versus only radiation in rural medical college. Material and Method: Histopathologically proven non-metastatic LAHNSCC were randomized into 2 arms. Patients in both arms initially received 3 cycles of NACT (inj Paclitaxel 175mg/m 2 and inj Carboplation AUC 6, i.v, q 21 days). Thereafter they received definitive treatment accordingly: arm A (control arm) received conventionally fractionated radiotherapy (CFRT), 70 Gy in 35 # and in arm B (study arm) received conventionally fractionated radiotherapy (CFRT), 70 Gy in 35 # with concomitant 3 weekly cisplatin 100mg/m 2. A RECIST v1.0 criterion was used for response assessment and toxicities evaluated by RTOG Acute and late Morbidity scorings.
Radiotherapy for cancer of the head and neck: altered fractionation regimens
The Lancet. Oncology, 2002
A greater understanding of radiobiology led to the development of two classes of radiation fractionation schedules for the treatment of head and neck cancers. The aim of accelerated fractionation is to reduce tumour proliferation, which is a major cause of relapse, by shortening the total duration of radiotherapy. By contrast, hyperfractionation exploits the differential sensitivity of tumour cells and normal tissues to radiation, to increase the therapeutic gain. The results of clinical trials of various types of altered fractionation schedules in head and neck carcinomas are examined in this review. Acceleration of radiation by 1 week without dose reduction and hyperfractionation are consistently better than standard fractionation for locoregional control of intermediate to advanced carcinomas without an increase in late toxic effects. However, improvement in survival of patients has not been consistent. Clinical investigations show that improvement in locoregional disease control and consistent gain in survival have been achieved with combinations of radiotherapy and concurrent chemotherapy in patients with mostly stage IV carcinomas. However, these benefits have been at the expense of increased late morbidity. Consequently, concurrent radiochemotherapy is now preferred for non-surgical treatment of patients with locally advanced carcinomas, whereas altered fractionation is generally selected for patients with intermediate-stage tumours or who are medically unfit to receive chemotherapy. Further data is needed before the combination of altered fractionation with chemotherapy can be recommended outside of a study setting.
Cancer Research Frontiers, 2017
Purpose: To review and summarize literature discussing the role of various altered fractionation schedules in head and neck squamous cell carcinoma (HNSCC). Methods and materials: Brief overview of pivotal clinical trials investigating the role of altered fractionation with conventional fractionation radiotherapy schedules in HNSCC patients treated with curative intent radiotherapy. Results: Overall, altered fractionation regimens have demonstrated improved outcomes in the curative treatment of HNSCC. Upon comparing different schedules, hyper-fractionated radiotherapy has shown more favorable impact with comparable survival advantage to that of concurrent chemo-radiotherapy. Although, the concept of integrating concurrent chemotherapy with altered fractionation is promising to improve control, it is at the cost of additional toxicity. Mild hypo-fractionation may be advantageous in achieving superior results in early glottic tumors. Conclusions: This summary is a compilation of large published clinical studies addressing biological rationale, evidence and clinical issues of various altered fractionation schedules and may be useful to facilitate clinician in treatment-decisions making in a clinical context.
IOSR Journal of Dental and Medical Sciences (IOSR-JDMS), 2022
Introduction: Locally advanced head and neck carcinomas constitute a substantial proportion of cancer patients in Bangladesh. The common practice is to treat the condition by conventional fractionation (2 gray/fraction, total dose 66 gray). Hypo-fractionated radiotherapy (2.75 gray/fraction, total 55 gray) might be able to produce a similar response in a shorter time. Aim of the study: The aim of the study was to determine tumor response and toxicities in hypo-fractionated radiotherapy. Methods: This Quasi-Experimental study was conducted at the Department of Oncology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, and the Department of Radiation Oncology, National Institute of Cancer Research & Hospital, Dhaka, Bangladesh. The study duration was 1.5 years, from July 2018 to December 2019. During this period, a total of 74 patients with inoperable locally advanced squamous cell carcinoma of the head and neck, and equally distributed in two groups, Arm-A and Arm-B. Arm-A received conventionally fractionated chemo-radiotherapy and Arm-B received hypo-fractionated radiotherapy Result: The mean age of Arm-A and B patients were 53.27 (±11.23) & 51.03 (±9.48) years, respectively. Among 74 patients, 46 patients were smokers. 33.68 % of patients were in stage III and 66.22% of patients were in stage IV. In Arm-A 10 patients (27.03%) showed a complete response and in Arm-B, a complete response was observed in 7 patients (18.93%). Partial response was 19 (51.35%) and 18 (48.64%) in Arm-A and B, respectively. There were 4 (10.81%) progressive disease cases in Arm-A and 5 (13.51%) in Arm-B. Significant differences in frequencies of acute grade 2 skin toxicity, mucositis, were found, with higher frequencies. Grade 2 oral mucositis was seen in 26 (70.27%) and 14 ( 37.83%) patients of Arm-A and B, respectively which was statistically significant. Other toxicities had no significant differences between Arm-A and B. in Arm-B. Conclusion: Hypo-fractionated radiotherapy can achieve a similar tumor response to conventionally fractionated radiotherapy in HNSCC, although with some increase of manageable toxicity.
International Journal of Radiation Oncology Biology Physics, 2000
Addition of thoracic radiation therapy (TRT) to chemotherapy (CHT) can increase overall survival in patients with small cell lung cancer limited-disease (SCLC-LD). Accelerated fractionation and early concurrent platinum-based CHT, in combination with prophylactic cranial irradiation, represent up-front treatment for this group of patients. Optimised and tailored local and systemic treatment is important. These concepts were applied when a new regional treatment programme was designed at Sahlgrenska University Hospital in 1997. The planned treatment consisted of six courses of CHT (carboplatin/etoposide)'TRT9prophylactic cranial irradiation (PCI). Standard TRT was prescribed as 1.5 Gy BID to a total of 60 Gy during 4 weeks, starting concomitantly with the second or third course of CHT. However, patients with large tumour burdens, poor general condition and/or poor lung function received 45 Gy, 1.5 Gy BID, during 3 weeks. PCI in 15 fractions to a total dose of 30 Gy was administered to all patients with complete remission (CR) and ''good'' partial remission (PR) at response evaluation. Eighty consecutive patients were treated between January 1998 and December 2004. Forty-six patients were given 60 Gy and 34 patients 45 Gy. Acute toxicity occurred as esophagitis grade III (RTOG/EORTC) in 16% and as pneumonitis grade I ÁII in10%. There were no differences in toxicity between the two groups. Three-and five-year overall survival was 25% and 16%, respectively. Median survival was 20.8 months with no significant difference between the two groups. In conclusion, TRT with a total dose of 60 or 45 Gy is feasible with comparable toxicity and no difference in local control or survival. Distant metastasis is the main cause of death in this disease; the future challenge is thus further improvement of the systemic therapy combined with optimised local TRT.