Novel approach of prophylactic radiation to reduce toxicities comparing 2-step40 with 56-Gy simultaneous integrated boost intensity-modulated radiation therapy for locally advanced squamous cell carcinoma of the head and neck, an intergroup phase III trial (JCOG1912, NEW BRIDGE).

BACKGROUND: Chemoradiotherapy (CRT) with concurrent cisplatin is the standard of care as a nonsurgical definitive treatment for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, CRT is associated with increased severe late adverse events, including swallowing dysfunction, xerostomia, ototoxicity, and hypothyroidism. Few strategies aimed at less invasive CRT without compromising treatment outcomes have been successful. The purpose of this study is to confirm the non-inferiority of reduced dose prophylactic radiation with 40 Gy compared to standard dose prophylactic radiation with 56 Gy in terms of the time to treatment failure (TTF) among patients with clinical stage III-IVB LA-SCCHN. METHODS: This study is a multicenter, two-arm, open-label, randomized phase III trial. Patients with LA-SCCHN excluding p16 positive oropharynx cancer are randomized to the standard arm or experimental arm. A total dose of 70 Gy for tumors with concurrent cisplatin at 100 mg/m2 are administered in both arms. For prophylactic field, patients in the standard arm receive a total dose of 56 Gy in 35 fractions for 7 weeks using simultaneous integrated boost (SIB56) and those in the experimental arm receive 40 Gy in 20 fractions using two-step methods for 4 weeks (2-step40). A total of 400 patients will be enrolled from 52 Japanese institutions within 5 years. The primary endpoint is TTF, and the secondary endpoints are overall survival, complete response rate, progression-free survival, locoregional relapse-free survival, acute and late adverse events, quality of life score, and swallowing function score. DISCUSSION: If the experimental arm is non-inferior to the standard arm in terms of TTF and superior on the safety endpoints, the 2-step40 procedure is the more useful treatment than SIB56 for definitive CRT. TRIAL REGISTRATION: This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031210100 ( https://jrct.niph.go.jp/latest-detail/jRCTs031210100 ). Date of Registration: May 2021.

Treatment strategy and outcomes in locally advanced head and neck squamous cell carcinoma: a nationwide retrospective cohort study (KCSG HN13-01).

BACKGROUND: By investigating treatment patterns and outcomes in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), we aimed at providing valuable insights into the optimal therapeutic strategy for physicians in real-world practice. METHODS: This is a multi-institutional study enrolled the patients with stage III to IVB LA-HNSCC, except for nasopharyngeal carcinoma, from 2004 to 2015 in thirteen referral hospitals capable of multidisciplinary care. RESULTS: A total of 445 LA-HNSCC patients were analyzed. The median age was 61 years (range, 24-89). The primary tumor location was the oropharynx in 191 (43%), oral cavity in 106 (24%), hypopharynx in 64 (14%), larynx in 57 (13%) and other sites in 27 (6%). The most common stage was T2 in 172 (39%), and N2 in 245 (55%). Based on treatment intents, 229 (52%) of the patients received definitive concurrent chemoradiotherapy (CCRT) and 187 (42%) underwent surgery. Approximately 158 (36%) of the study population received induction chemotherapy (IC). Taken together, 385 (87%) of the patients underwent combined therapeutic modalities. The regimen for definitive CCRT was weekly cisplatin in 58%, 3-weekly cisplatin in 28% and cetuximab in 3%. The preferred regimen for IC was docetaxel with cisplatin in 49%, and docetaxel, cisplatin plus fluorouracil in 27%. With a median follow-up of 39 months, one-year and two-year survival rates were 89 and 80%, respectively. Overall survival was not significantly different between CCRT and surgery group (p = 0.620). CONCLUSIONS: In patients with LA-HNSCC, the majority of patients received combined therapeutic modalities. Definitive CCRT, IC then definitive CCRT, and surgery followed by adjuvant CCRT or radiotherapy are the preferred multidisciplinary strategies in real-world practice.

Therapeutic Intensification and Induction Chemotherapy for High-Risk Locally Advanced Squamous Cell Carcinoma.

OPINION STATEMENT: The treatment of HNSCC has rapidly evolved over the past 30 years and multidisciplinary management is required, especially for locally advanced disease (LAHNSCC). Concomitant chemoradiation (cCRT) is the standard of care and cetuximab/RT (CET/RT) is an alternative treatment option, especially for patients unfit for concurrent cisplatin. Several intensification strategies have been explored to improve the outcome of the concomitant treatment. The combination of cisplatin plus cetuximab concurrent to RT failed to improve overall survival (OS) in two phase III trials. Induction chemotherapy (IC) has a proven role in organ preservation; however, its ability in prolonging OS has not been clearly demonstrated. Immune checkpoint inhibitors (ICIs), specifically anti PD-1 inhibitors, have been recently approved for the treatment of patients with recurrent/metastatic platinum-refractory disease. Recent clinical trials are exploring the role of immunotherapy at earlier stages of the disease in combination with concomitant treatments. The purpose of this article is to review current evidence regarding treatment intensification strategies for LAHNSCC (except nasopharyngeal carcinomas) with particular emphasis on the role of induction chemotherapy.

Quality of life of patients with locally advanced head and neck cancer treated with induction chemotherapy followed by cisplatin-containing chemoradiotherapy in the Dutch CONDOR study: a randomized controlled trial.

PURPOSE: The CONDOR study showed that docetaxel/cisplatin/5-fluorouracil (TPF) followed by conventional radiotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 (cis100 + RT; n = 27)) versus accelerated radiotherapy with cisplatin weekly 40 mg/m2 (cis40 + ART; n = 29) in locally advanced head and neck cancer (LAHNC) patients was not feasible. Here, we report the analysis of health-related quality of life (HRQOL) of the patients entered in this study. METHODS: HRQOL was assessed at baseline, after two TPF, before start of chemoradiotherapy, and 1, 4, 8, 12, and 24 months after completion of chemoradiotherapy using the EORTC-QLQ-C30 and QLQ-H&N35 in 62 patients. RESULTS: Compliance with the QOL questionnaires was 94% (59/62) at baseline and 61% (30/49) at 12 months, respectively. HRQOL decreased after TPF and further decreased during chemoradiohteray in both arms equally. Pain and swallowing dysfunction improved significantly during TPF but deteriorated below baseline levels during chemoradiotherapy, cis40 + ART > cis100 + RT (p < 0.05). HRQOL and symptoms restored to baseline within 12 months in both arms and remained at that level until 24 months. CONCLUSIONS: After TPF, cis40 + ART had a larger negative impact on symptoms than cis100 + RT, probably due to the ART. HRQOL and symptoms restored to baseline levels within 12 months after end of treatment in both arms, which is an important perspective for patients during the phase of most serious acute side effects of treatment. TRIAL REGISTRATION: NCT00774319.

18F-Fluorodeoxyglucose-PET/CT in locally advanced head and neck cancer can influence the stage migration and nodal radiation treatment volumes.

AIM: To analyze the impact of 18F-fluorodeoxyglucose-PET/CT (PET/CT) in the radiotherapy (RT) planning strategy in HNC, correlating CT-scan and PET/CT performances. MATERIALS AND METHODS: Inclusion criteria were: age >18 years old, histologically proven head and neck cancer (HNC), patients candidate to definitive RT ± chemotherapy, stage of disease by means of PET/TC and CT-scan performed at our Cancer Care Center. RESULTS: Sixty patients were analyzed. The following primary tumor sites were investigated: nasopharynx (13%), oropharynx (42%), oral cavity (32%) and larynx non-glottic (13%). Globally, PET/CT findings caused changes on nodal radiation treatment volumes in 10% of all the population of study. Specifically, in 5 cases out of 19 oral cavity tumors (26%), PET/CT detected neck-nodes positive (not detected at CT-scan). These findings have allowed to change the patients management, including PET/CT neck-nodes positive in the high-risk RT volumes. CONCLUSION: In the RT planning strategy, the present findings support the use of PET/CT to improve upfront regional staging of HNC disease, particularly for oral cavity tumors. Further investigations are advocated to evaluate if this strategy could impact on long-term outcomes in terms of local control and overall survival.

Sequential TPF chemotherapy followed by concurrent chemoradiotherapy in locally advanced head and neck cancer--a retrospective analysis of toxicity and outcomes.

BACKGROUND AND AIMS: Phase III trials have shown that the addition of a taxane to cisplatin/5FU-based induction chemotherapy (TPF) improves response rates and overall survival in unresectable stage III/IV head and neck cancer. We sought to assess the tolerability, compliance and clinical outcomes of this treatment regime. METHODS: A retrospective study of patients treated within a single centre between September 2007 and November 2010. Toxicities were graded according to CTCAE version 3.0. Survival, distant metastasis and local control rates are expressed as percentages at two years using the Kaplan-Meier method. RESULTS: A total of 100 patients were identified (11% stage III, 86% stage IV) and 32% of patients were admitted as an emergency after TPF. The rate of neutropenic fever was 31%, this number fell to 9% when prophylactic G-CSF was used. In addition, 89% of patients underwent radical chemoradiation. Of these, 96% completed the full radiotherapy course. However, only 64% of patients received a minimum of two cycles of concurrent platinum chemotherapy. The two-year overall survival, metastasis free survival and local control rates were 62.6%, 88.5% and 73.3%, respectively. CONCLUSIONS: TPF chemotherapy can be delivered safely in a non-trial cohort of patients. There is, however, a significant reduction in concurrent chemotherapy dose intensity. The long-term impact of this remains unclear.

Treatment outcomes of standard (high dose) cisplatin and non-standard chemotherapy for locally advanced head and neck cancer.

INTRODUCTION: Concurrent chemoradiotherapy with high-dose (HD) cisplatin is the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Due to the higher treatment-related adverse effects with standard therapy, alternative regimens (non-standard therapy), namely, lower dose weekly cisplatin, carboplatin/paclitaxel, or cetuximab are considered. There is, however, no consensus on non-standard regimens. We aimed to investigate the efficacy and safety profile of these regimens. METHODS: This single centre retrospective cohort study included all consecutive adult patients with newly diagnosed LA-HNSCC treated with either standard or non-standard regimens between January 2016 and April 2021. The primary outcome was 2-year failure-free survival (FFS). The secondary outcomes included acute toxicities, hospitalisation rates, dose modifications, treatment failure rates (TFR), and overall survival. RESULTS: About 235 patients were included in the final analysis; median age was 61 years (IQR 55-67), and 87% were male. Most had oropharyngeal tumours (85.5%) and p16-positivity was frequent (80%). About 56% received non-standard regimens: weekly cisplatin = 79 and non-cisplatin = 48. These patients had higher Charlson Comorbidity Index (CCI; p < .001) and lower European Cooperative Oncology Group (ECOG)-0 (p = .003). There was no difference in 2-year FFS (hazard ratio [HR] = 1.16; 95% confidence interval - [CI] 0.65-2.05), hospitalisation and grade-3 toxicity rates between the two regimens. Nausea and vomiting were lower in the non-standard regimen (3.0% vs. 16%, p < .001). Dose reductions, adjusted for age, sex, and CCI, were less likely in the non-standard regimen (OR = 2.36; 95%-CI: 1.01-5.49, p = .007). CONCLUSIONS: We demonstrated similar efficacy of lower dose weekly cisplatin and carboplatin/paclitaxel regimens and better safety profile of weekly cisplatin compared to standard HD cisplatin regimens for LA-HNSCC. Multicenter randomised control trials are required in HD cisplatin-ineligible patients.

Concurrent carboplatin and paclitaxel definitive radiation therapy for locally advanced head and neck cancer.

BACKGROUND: We report the outcomes of cisplatin-ineligible HNSCC patients treated with definitive chemoradiation and concurrent carboplatin and paclitaxel. MATERIALS AND METHODS: We included consecutive HNSCC patients treated from 2013 to 2021 that received definitive chemoradiation with carboplatin and paclitaxel. Locoregional recurrences (LRR) and distant metastases (DM) were estimated using cumulative incidence functions. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. RESULTS: Sixty-five patients were identified with median age of 71 years (range 44-85). Median radiation dose was 70 Gy and the median doses of carboplatin and paclitaxel were AUC 1 and 40 mg/m2 , respectively. At a median follow-up of 29 (range 5-91) months, the 2-year rates of LRR, DM, PFS, and OS were 8.8%, 9.4%, 72.2%, and 88.7%, respectively. In total, there were 5 LRR, 7 DM, and 12 deaths. CONCLUSIONS: Chemoradiation with carboplatin and paclitaxel is an excellent option for cisplatin-ineligible HNSCC patients.

Induction chemotherapy in head and neck cancer - Boon or bane?

Introduction: Although concurrent chemoradiotherapy is the standard of care for inoperable locally advanced head and neck cancer, induction chemotherapy is considered an alternative approach by head and neck oncologists worldwide. Aims: To evaluate the response to induction chemotherapy in terms of loco-regional control and treatment-related toxicity in inoperable locally advanced head and neck cancer patients. Materials and Methods: This prospective study was conducted on patients who received two to three cycles of induction chemotherapy. Following this, response assessment was performed clinically. Grading of radiation-induced oral mucositis and any interruptions in treatment were noted. At 8 weeks following treatment, magnetic resonance imaging-based radiological response assessment was performed using RECIST criteria version 1.1. Results: Our data revealed 57.7% complete response rate with induction chemotherapy, followed by chemoradiation therapy. We observed that post induction, 67.5% and 47.5% patients had reduction in T-stage (<0.001) and N-stage of disease (<0.001), respectively, with complete response more achieved in younger patients (≤50 years). Chemotherapy-induced bone marrow suppression and febrile neutropenia occurred in 7.5% patients. We demonstrated that a higher grade of radiation-induced mucositis was noticed among those receiving three cycles of induction chemotherapy (ICT) and aged >50 years. Conclusion: We conclude that induction chemotherapy could still be a viable option for down-staging unresectable locally advanced disease, especially for younger patients in terms of better treatment response and tolerability. The number of cycles of ICT seems to influence radiation-induced mucositis. This study underscores the need for further studies to determine the exact role of ICT in locally advanced head and neck cancer.

Quality of life and its correlates in pretreatment patients with locally advanced head and neck cancer: A cross-sectional study in Thailand.

Background: Locally advanced head and neck cancer (LAHNC) can significantly impact the quality of life of patients in various ways. However, several factors can contribute to the decrease in quality of life. In Thailand, there is limited knowledge about the factors that affect the quality of life of patients with LAHNC before they receive treatment. Objective: This study aimed to examine the correlations between Palliative Performance Scale (PPS), family income, body mass index (BMI), age, comorbidity index, and the quality of life of patients with LAHNC before they undergo treatment. Methods: A correlational cross-sectional study was conducted, and data were collected from 94 pretreatment patients with LAHNC who were admitted to a cancer center in central Thailand using purposive sampling. The data collection instruments included a demographic data form, a medical record form, the Charlson Comorbidity Index (CCI), the Palliative Performance Scale (PPS), and the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) version 4. Descriptive statistics, Pearson's correlation, and Spearman's rank correlation were used to analyze the data. Results: All study participants completed the questionnaire. The results showed that the overall quality of life of the patients was moderate. PPS, family income, and body mass index were moderately positively correlated with quality of life (r = 0.494, p <0.01; r = 0.420, p <0.01; r = 0.339, p <0.01, respectively). Age had a moderate negative correlation with quality of life (r = -0.596, p <0.01), while comorbidity was not significantly associated with quality of life. Conclusion: The quality of life of patients with LAHNC before treatment was associated with various factors, including PPS, family income, body mass index, and age. These findings highlight the importance of nutritional support before treatment and the need for social support, especially for older adult patients, to improve their quality of life. The results of this study can be valuable for nurses in developing care programs that enhance the quality of life for patients with LAHNC during the pretreatment phase.

A Comparison of the Toxicities in Patients With Locally Advanced Head and Neck Cancers Treated With Concomitant Boost Radiotherapy Versus Conventional Chemoradiation.

PURPOSE: To compare the objective and patient-reported toxicities of concomitant boost radiotherapy (CBRT) and concurrent chemoradiation (CRT) in patients with locally advanced head and neck cancers. METHODS AND MATERIAL: In this prospective study, 46 patients with histologically proven stage III-IVA head and neck cancer were randomly assigned to receive either concurrent chemoradiation to a dose of 66 Gy in 33 fractions over 6.5 weeks with concurrent cisplatin (40 mg/m2 IV weekly; control arm) or accelerated radiotherapy with concomitant boost radiotherapy (study arm) to a dose of 67.5 Gy in 40 fractions in five weeks. Acute toxicity was evaluated using RTOG toxicity criteria. The assessment was done weekly after initiation of treatment, at the first follow-up (six weeks), and at three months. The four main patient-reported symptoms of pain, hoarseness of voice, dryness of mouth, and loss of taste were also compared between the two groups to assess patient quality of life during treatment. RESULTS: The mean treatment duration was 37 days in the CBRT arm and 49 days in the CRT arm. Treatment-related interruptions were less in the study group,17.3% in the study, and 27.2% in the control with insignificant P-value. Grade III laryngeal toxicity was significantly higher in the study group (P=0.029). Other acute grade I-III toxicities (pharyngeal, skin, mucositis, and salivary) were comparable in both CRT and CBRT arms. Grade IV toxicities were seen only in the CBRT arm but were resolved at the first follow-up. Haematological toxicities and renal toxicities were significantly higher in the CRT arm, with significant P-values of 0.0004 and 0.018, respectively. CONCLUSION: In patients with locally advanced head and neck cancer, concomitant boost radiotherapy is well tolerated with acceptable local toxicity and minimal systemic toxicity as compared to conventional chemoradiation. It is a feasible option for patients with locally advanced head and neck cancer not fit for concurrent chemoradiation.

Diagnostic challenges and prognostic implications of extranodal extension in head and neck cancer: a state of the art review and gap analysis.

Extranodal extension (ENE) is a pattern of cancer growth from within the lymph node (LN) outward into perinodal tissues, critically defined by disruption and penetration of the tumor through the entire thickness of the LN capsule. The presence of ENE is often associated with an aggressive cancer phenotype in various malignancies including head and neck squamous cell carcinoma (HNSCC). In HNSCC, ENE is associated with increased risk of distant metastasis and lower rates of locoregional control. ENE detected on histopathology (pathologic ENE; pENE) is now incorporated as a risk-stratification factor in human papillomavirus (HPV)-negative HNSCC in the eighth edition of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) TNM classification. Although ENE was first described almost a century ago, several issues remain unresolved, including lack of consensus on definitions, terminology, and widely accepted assessment criteria and grading systems for both pENE and ENE detected on radiological imaging (imaging-detected ENE; iENE). Moreover, there is conflicting data on the prognostic significance of iENE and pENE, particularly in the context of HPV-associated HNSCC. Herein, we review the existing literature on ENE in HNSCC, highlighting areas of controversy and identifying critical gaps requiring concerted research efforts.

Efficacy and feasibility of Apatinib and S-1 as a novel oral induction therapy in locally advanced head and neck squamous cell carcinoma: an exploratory phase 2 open-label, single-arm trial.

Objectives: The current standard nonsurgical treatment for locally advanced head and neck squamous cell cancer (LA-HNSCC) is concomitant chemoradiotherapy (CRT). Neoadjuvant chemotherapy combined with CRT has been explored in HNSCC patients and is an acceptable strategy. However, the occurrence of adverse events (AEs) restricts its application. We conducted a clinical study to explore the efficacy and feasibility of a novel induction therapy with orally administered apatinib and S-1 in LA-HNSCC. Materials and methods: This nonrandomized, single-arm, prospective clinical trial included patients with LA-HNSCCs. The eligibility criteria included histologically or cytologically confirmed HNSCC, with at least one radiographically measurable lesion detected by magnetic resonance imaging (MRI) or computerized tomography (CT) scan, age 18-75 years, and a diagnosis of stage III to IVb according to the 7th edition of the American Joint Committee of Cancer (AJCC). Patients received induction therapy with apatinib and S-1 for three cycles (3 weeks/cycle). The primary endpoint of this study was the objective response rate (ORR) to induction therapy. The secondary endpoints included progression-free survival (PFS), overall survival (OS), and AEs during induction treatment. Results: From October 2017 to September 2020, 49 patients with LA-HNSCC were screened consecutively and 38 were enrolled. The median age of the patients was 60 years (range, 39-75). Thirty-three patients (86.8%) had stage IV disease according to the AJCC staging system. The ORR after induction therapy was 97.4% (95% confidence interval [CI]: 86.2%-99.9%). the 3-year OS rate was 64.2% (95% CI: 46.0%-78.2%) and 3-year PFS was 57.1% (95% CI: 40.8%-73.6%). The most common AEs during induction therapy were hypertension and hand-foot syndrome, which were manageable. Conclusion: Apatinib combined with S-1 as novel induction therapy for LA-HNSCC patients resulted in a higher-than-anticipated ORR and manageable adverse effects. With the associated safety profile and preferable oral administration route, apatinib combined with S-1 is an attractive exploratory induction regimen in outpatient settings. However, this regimen failed to show a survival benefit. Clinical trial registration: https://clinicaltrials.gov/show/NCT03267121, identifier NCT03267121.

Comparative study of induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone in locally advanced head and neck cancer.

Objective: Concurrent chemoradiotherapy (CTRT) is the standard treatment for patients with unresectable, nonmetastatic Locally advanced squamous cell cancer of head and neck (LASCCHN). The aim of this study to compare the efficacy and toxicity of induction chemotherapy (ICT) followed by CTRT versus standard CTRT alone in patients with LASCCHN. Materials and Methods: Between January 2017 and September 2017, 100 patients with LASCCHN (Stage III and IV) were randomly assigned to two arms: 50 patients in each. Arm A treated by standard CTRT alone (a total 66 Gy in 33fr 2 Gy/# administered daily 5 days/week with 3 weekly inj. cisplatin 100 mg/m2 divided in two days) and Arm B received two cycles of ICT (TPF - inj. paclitaxel 175 mg/m2 on day 1, cisplatin 100 mg/m2 divided in 2 days and inj. 5FU 1 gm/m2 iv d1 and d2 ) followed by same CTRT. Assessment was done weekly during RT and 1, 3, 6, 12, and 18 months posttreatment for treatment response, toxicities, and progression-free survival (PFS). Results: Total response was observed 79.1% and 82.1% in Arm A and Arm B, respectively (P = 0.705) at 6-8 weeks after the completion of treatment. Acute toxicities were significantly higher in ICT arm. The 18 months PFS was 57% versus 55% in Arm A and Arm B, respectively (x2 = 0.039, P = 0.8414). Conclusion: Among the patients followed, this study failed to show benefit of ICT-CTRT over CTRT alone in patients of LASCCHN.

Assessment of the Role of Gefitinib With Concurrent Chemoradiation in Locally Advanced Head and Neck Cancer.

BACKGROUND: The treatment of locally advanced head and neck carcinoma has been a combination of chemotherapy and radiation. The higher incidences of recurrence and metastasis warrant the search for an alternative therapy for better patient outcomes. This study was designed to evaluate the effect of gefitinib in conjunction with concurrent chemoradiation in locally advanced stages III and IV head and neck cancer. METHODOLOGY: The patients were equally divided into two groups: Group I received cisplatin 100 mg/m2 on the first, 22nd, and 43rd days together with the radiation, whereas Group II was given the same treatment as Group I together with oral doses of gefitinib 250 mg on a daily basis, starting two weeks prior to radiotherapy and continuing until the completion of it. The dose of radiotherapy was 2 Gray (Gy) per fraction given over a period of five days per week to a maximum of 70 Gy in locally higher grades of head and neck neoplasms. The evaluation was performed in accordance with the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, which include stable disease (SD), progressing disease (PD), partial response (PR), and complete response (CR). Salvage chemotherapy, potential surgical intervention, or palliative care was presented to patients with remaining or recurring diseases. The grading of the patients for acute and chronic radiation morbidity was done according to the Radiation Therapy Oncology Group (RTOG) criteria for toxicity during radiation treatment and at each subsequent follow-up. Parameters such as site, nodal involvement, stage, tumor status, and Eastern Cooperative Oncology Group (ECOG) were recorded. RESULTS: On comparing the patient characteristics, no statistical significance was observed. The overall response was seen in 24 (80%) and 28 (83.33%) patients in Group I and Group II, respectively (p = 0.08). All patients in Group I and Group II reported xerostomia as an acute/chronic adverse event of chemotherapy. Similarly, mucositis, dysphagia, and diarrhea were observed in all the patients, and no statistical difference was observed. Seventeen (56.67%) patients in Group II had complaints of skin rashes, while four (13.33%) patients in Group I had similar complaints (p = 0.01). CONCLUSION: The study concludes that encouraging results were observed in comparing overall response after the addition of oral gefitinib to the traditional treatment of locally advanced head and neck neoplasms.

Accelerated Fractionation With Concomitant Boost vs. Conventional Radio-chemotherapy for Definitive Treatment of Locally Advanced Squamous Cell Carcinoma of the Head-and-Neck (SCCHN).

BACKGROUND/AIM: Patients with unresectable head-and-neck cancer (SCCHN) unable to tolerate radiochemotherapy may receive unconventionally fractionated radiotherapy. This retrospective study compared both treatments. PATIENTS AND METHODS: Eight patients unsuitable for chemotherapy were assigned to accelerated fractionation with concomitant boost (AF-CB, 69.6 Gy/39 fractions) over 5.5 weeks (group A) and 72 patients to cisplatin-based radiochemotherapy (70 Gy/35 fractions) over 7 weeks (group B). Groups were matched (cancer site, gender, age, performance score, T-/N-stage, histologic grade) and compared for loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS) and toxicities. RESULTS: LRC, MFS, OS and radiation-related toxicities were not significantly different between groups A and B. Improved outcomes were associated with favorable cancer site, better performance score and T3-stage. In group B, toxicity led to reduction/discontinuation of chemotherapy in 38.9% and interruptions of radiotherapy >7 days in 19.3% of patients. CONCLUSION: AF-CB appeared a reasonable alternative for patients who cannot safely receive radio-chemotherapy for unresectable SCCHN.

The impact of age on outcome in phase III NRG Oncology/RTOG trials of radiotherapy (XRT) +/- systemic therapy in locally advanced head and neck cancer.

PURPOSE: To examine the role age plays in the treatment and prognosis of locally advanced head and neck cancer (LAHNC) treated definitively with radiation alone or combined modality therapy. METHODS: A retrospective analysis was performed of three NRG/RTOG trials examining either radiation alone or combined radiation and systemic therapy for LAHNC. The effect of age (≥70 yrs.) on cause-specific survival (CSS), overall survival (OS), and toxicity was evaluated. RESULTS: A total of 2688 patients were analyzed, of whom 309 patients (11.5%) were ≥ 70. For all studies combined, the hazard ratio (HR) for CSS for patients age ≥ 70 vs. those <70 was 1.33 (95%CI: 1.14-1.55, p < 0.001). For OS, the HR for patients age ≥ 70 vs. those <70 for all studies combined was 1.55 (95% CI 1.35-1.77, p < 0.001). After adjustment for all covariates, age ≥ 70 was associated with worse OS regardless of adjustment for smoking and p16 status. The survival difference was more pronounced in those receiving combined radiation and systemic therapy. Hematologic and renal toxicities were increased in combined modality trials in patients ≥70 years old. CONCLUSIONS: Patients age ≥ 70 with LAHNC were underrepresented in these clinical trials. Their CSS and OS proved inferior to patients <70 years old.

Palliative radiotherapy in older adults with head and neck squamous cell carcinoma: A systematic review.

Locally advanced Head and neck squamous cell carcinoma (SCCHN) represents a common oncologic pathology in older adults (OA). While radiotherapy represents a cornerstone in this context, it is unclear what is the optimal radiation regimen for SCCHN in the palliative setting, especially for OA. This article addresses issues related to palliative radiotherapy (PRT) in this setting with a focus on treatment modalities and toxicity. We also explore the use of quality of life and geriatric assessment in this setting. Medline, Scopus and Embase databases were queried for articles in this setting. We included studies published from January 1, 2000 through June 1, 2020, that were independently evaluated by two authors. Analyzed endpoints were progression free survival (PFS), overall survival (OS) and PRT toxicities. The meta-analysis was performed using Stata v.14. A total of 33 studies were included in this meta-analysis. The pooled median OS is 7.7 months, 2-years OS was worse for higher radiation dose (p = 0.02). The pooled median PFS was 5.4 months, PFS was influenced by EQD2 (p = 0.01), with patients receiving an EQD2 < 40 Gy that presented a poorer outcome. Regarding acute toxicities, most common pooled G3 toxicities were mucositis (7%) and dysphagia (15%). Among late toxicity, most common G3 toxicity was dysphagia in 7% of patients. Radiotherapy should be the most effective palliative treatment in symptomatic SCCHN OA. A tailored approach, guided by geriatric tools, would be indicated to choose the right therapy.

Early Loss of Fat Mass During Chemoradiotherapy Predicts Overall Survival in Locally Advanced Squamous Cell Carcinoma of the Lung, but Not in Locally Advanced Squamous Cell Carcinoma of the Head and Neck.

Background: Cancer cachexia is highly prevalent in advanced non-small cell lung cancer (NSCLC) and locally advanced head and neck squamous cell carcinoma (LAHNSCC), and compromises treatment tolerance and overall survival (OS). NSCLC and LAHNSCC patients share similar risk factors, and receive comparable anti-cancer treatment regimens. The aim of this study was to determine the predictive value of body composition assessed by bioelectrical impedance analysis (BIA) and handgrip strength (HGS) (baseline and early changes during therapy) on OS in NSCLC and LAHNSCC patients treated with platinum-based chemoradiotherapy (CRT) or cetuximab-based bioradiotherapy (BRT). To elucidate potential underlying determinants of early changes in body composition and HGS, specific (fat and fat free) mass loss patterns of squamous NSCLC (sNSCLC) were compared to human papilloma virus negative (HPV-) LAHNSCC patients treated with CRT. Methods: Between 2013 and 2016, BIA and HGS were performed at baseline and after 3 weeks of CRT/BRT in LAHNSCC and NSCLC patients treated with curative intent. Results: Two hundred thirty-three patients were included for baseline measurements. Fat free mass index (FFMI) and HGS<10th percentile of reference values at baseline were both prognostic for poor OS in NSCLC and LAHNSCC [HR 1.64 [95%CI 1.13-2.39], p = 0.01 and HR 2.30 [95%CI 1.33-3.97], p = 0.003, respectively], independent of Charlson Comorbidity Index, cancer site, and gross tumor volume. Early fat mass (FM) loss during CRT was predictive for poor OS in sNSCLC (n = 64) [HR 3.80 [95%CI 1.79-8.06] p ≤ 0.001] but not in HPV- LAHNSCC (n = 61). In patients with significant weight loss (>2%) in the first 3 weeks of CRT (sNSCLC n = 24, HPV- LAHNSCC n = 23), the FM change was -1.4 ± 14.5% and -8.7 ± 9.0% in sNSCLC and HPV- LAHNSCC patients, respectively (p < 0.05). Fat fee mass change was -5.6 ± 6.3% and -4.0 ± 4.3% for sNSCLC and HPV- LAHNSCC, respectively (p = 0.31). Conclusion: FFMI and HGS<10th percentile at baseline are independent prognostic factors for poor OS in NSCLC and LAHNSCC patients treated with CRT/BRT. The specific composition of mass loss during first 3 weeks of CRT significantly differs between sNSCLC and HPV- LAHNSCC patients. Early FM loss was prognostic in sNSCLC only.

Randomized Controlled Study Comparing Efficacy and Toxicity of Weekly vs. 3-Weekly Induction Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma.

Background: Head and Neck Cancer is a major public health problem in India, majority of which are lifestyle related, male predominant requiring dedicated infrastructure and human resource. The 5-year survival is 59% for all stages combined and only 45% in patients with locally advanced inoperable head and neck cancer using current chemoradiation schedules. Chemotherapy agents administered in the induction or concurrent setting comprise of taxanes (Docetaxel, paclitaxel), platinum compounds (Cisplatin, carboplatin) and fluorouracil (TPF). For patients with advanced Head and neck squamous cell carcinoma (HNSCC), 3-weekly TPF regimen is the established standard induction chemotherapy (ICT) option based on overall survival benefit. However, TPF regimen is known to be associated with significant dose limiting toxicities which may impair tolerance and effectiveness of therapy. In this study we assessed the efficacy and toxicity of weekly vs. 3-weekly Docetaxel, Cisplatin, and Fluoro-uracil (TPF) induction chemotherapy in locally advanced Head and neck squamous cell carcinoma (LA-HNSCC). Methods: This was an open labeled randomized two arm study with 41 patients in the 3-weekly TPF arm and 41 patients in the weekly arm. Patients were randomized using numbers from a randomization software, data recorded, and results were analyzed. Results: The weekly group achieved far greater symptom relief than 3-weekly group (72 vs. 64%). The overall response rates were similar in both arms (ORR 75.6 and 73.1% in the weekly and 3-weekly groups, respectively). Renal toxicity was significantly lower in the weekly group as compared to 3 weekly arm post three cycles of chemotherapy (CrCl 91.49 ml/min vs. 76.67 ml/min, respectively). The weekly group had predominantly grade I and II neutropenia (19.5 and 17.1%, respectively) as compared to 3-weekly group where grade III and IV neutropenia (31 and 12%, respectively) was more prominent (p-0.003). Among non-hematological toxicities, mucositis, nausea/vomiting, and diarrhea in the weekly group were significantly lower when compared to 3-weekly group. Progression free survival was slightly higher in the weekly group (18 months) when compared to 3-weekly group (15 months) which was not statistically significant. Conclusion: Weekly induction with TPF had lower toxicity and similar efficacy as compared to 3-weekly regimen in locally advanced HNSCC patients. Myelosuppression, which was the most serious and common complication of 3-weekly TPF regimens was notably low using the weekly regimen. Our results suggest that weekly TPF regimen may be a safer and effective alternative to 3-weekly TPF for treatment of LA-HNSCC. To our knowledge this is the first study reporting the efficacy of weekly TPF regimen in LA-HNSCC till date.