Trigeminal Neuralgia in Advanced Head and Neck Cancer: A Complex Palliative Care Case.

Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by paroxysms of electric shock-like or stabbing pain in the face. This condition is associated with poor quality of life. First-line treatment includes carbamazepine or oxcarbazepine, but some cases show refractory symptoms to this approach. We describe a challenging case of secondary TN due to an advanced head and neck cancer managed by a palliative care team.

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.

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.

Impact of comorbidities on outcomes in patients with advanced head and neck cancer undergoing immunotherapy.

OBJECTIVES: To explore the impact of pre-existing comorbidities on immunotherapy response, overall and progression-free survival, and immune-related adverse events (irAEs) of patients with advanced head and neck cancer (HNC) treated with immunotherapy. PATIENTS AND METHODS: Ninety-three patients treated with immunotherapy were identified and stratified into comorbidity absent or present (CCI < 1 and CCI ≥ 1, respectively) cohorts, and clinical outcomes were compared between these two groups. RESULTS: Patients with no comorbidities had longer overall survival (aHR = 2.74, 95% CI [1.18, 6.40], p = 0.02) and progression-free survival (aHR = 2.07, 95% CI [1.03, 4.16], p = 0.04) and a higher tumor response rate (32% in CCI < 1 vs. 14% in CC ≥ 1, p = 0.05). Risk for irAEs was higher in the comorbidity absent group (p = 0.05). CONCLUSION: Comorbidity should be considered as a significant prognostic factor in clinical decision-making for patients with advanced HNC undergoing immunotherapy.

Eligibility for Photoimmunotherapy in Patients with Unresectable Advanced or Recurrent Head and Neck Cancer and Changes before and after Systemic Therapy.

Photoimmunotherapy is a novel cancer treatment that recently became covered by national health insurance in Japan, but treatment decision-making remains challenging for unresectable advanced or recurrent head and neck cancer. We aimed to clarify the characteristics of patients for whom photoimmunotherapy was indicated by a retrospective chart review. Patients aged ≥20 years diagnosed with advanced or recurrent head and neck cancer who started receiving systemic therapy at the National Cancer Center Hospital East from January 2016 through December 2020 were retrospectively analyzed. Before and after first-line systemic therapy, patients were classified into 3 groups according to eligibility for photoimmunotherapy: eligible, potentially eligible, and ineligible. In total, of 246 patients evaluated-194 after exclusions were analyzed-108 were deemed ineligible for treatment. Of the remaining 86 patients, 8 were considered potentially eligible and 9 eligible. Of the nine eligible patients, four became ineligible after receiving first-line systemic therapy due to disease progression. Our results suggest that the indication of photoimmunotherapy should be considered before, during, and after systemic therapy for unresectable locally advanced or recurrent head and neck cancer.

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.

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.

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.

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.

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.

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.

Knowledge-Based Planning for Robustly Optimized Intensity-Modulated Proton Therapy of Head and Neck Cancer Patients.

PURPOSE: To assess the performance of a proton-specific knowledge-based planning (KBP) model in the creation of robustly optimized intensity-modulated proton therapy (IMPT) plans for treatment of advanced head and neck (HN) cancer patients. METHODS: Seventy-three patients diagnosed with advanced HN cancer previously treated with volumetric modulated arc therapy (VMAT) were selected and replanned with robustly optimized IMPT. A proton-specific KBP model, RapidPlanPT (RPP), was generated using 53 patients (20 unilateral cases and 33 bilateral cases). The remaining 20 patients (10 unilateral and 10 bilateral cases) were used for model validation. The model was validated by comparing the target coverage and organ at risk (OAR) sparing in the RPP-generated IMPT plans with those in the expert plans. To account for the robustness of the plan, all uncertainty scenarios were included in the analysis. RESULTS: All the RPP plans generated were clinically acceptable. For unilateral cases, RPP plans had higher CTV_primary V100 (1.59% ± 1.24%) but higher homogeneity index (HI) (0.7 ± 0.73) than had the expert plans. In addition, the RPP plans had better ipsilateral cochlea Dmean (-5.76 ± 6.11 Gy), with marginal to no significant difference between RPP plans and expert plans for all other OAR dosimetric indices. For the bilateral cases, the V100 for all clinical target volumes (CTVs) was higher for the RPP plans than for the expert plans, especially the CTV_primary V100 (5.08% ± 3.02%), with no significant difference in the HI. With respect to OAR sparing, RPP plans had a lower spinal cord Dmax (-5.74 ± 5.72 Gy), lower cochlea Dmean (left, -6.05 ± 4.33 Gy; right, -4.84 ± 4.66 Gy), lower left and right parotid V20Gy (left, -6.45% ± 5.32%; right, -6.92% ± 3.45%), and a lower integral dose (-0.19 ± 0.19 Gy). However, RPP plans increased the Dmax in the body outside of CTV (body-CTV) (1.2 ± 1.43 Gy), indicating a slightly higher hotspot produced by the RPP plans. CONCLUSION: IMPT plans generated by a broad-scope RPP model have a quality that is, at minimum, comparable with, and at times superior to, that of the expert plans. The RPP plans demonstrated a greater robustness for CTV coverage and better sparing for several OARs.

Relevance of the time interval between surgery and adjuvant radio (chemo) therapy in HPV-negative and advanced head and neck carcinoma of unknown primary (CUP).

INTRODUCTION: In contrast to head and neck squamous cell carcinoma (HNSCC), the effect of treatment duration in HNSCC-CUP has not been thoroughly investigated. Thus, this study aimed to assess the impact of the time interval between surgery and adjuvant therapy on the oncologic outcome, in particular the 5-year overall survival rate (OS), in advanced stage, HPV-negative CUPs at a tertiary referral hospital. 5-year disease specific survival rate (DSS) and progression free survival rate (PFS) are defined as secondary objectives. MATERIAL AND METHODS: Between January 1st, 2007, and March 31st, 2020 a total of 131 patients with CUP were treated. Out of these, 59 patients with a confirmed negative p16 analysis were referred to a so-called CUP-panendoscopy with simultaneous unilateral neck dissection followed by adjuvant therapy. The cut-off between tumor removal and delivery of adjuvant therapy was set at the median, i.e. patients receiving adjuvant therapy below or above the median time interval. RESULTS: Depending on the median time interval of 55 days (d) (95% CI 51.42-84.52), 30 patients received adjuvant therapy within 55 d (mean 41.69 d, SD = 9.03) after surgery in contrast to 29 patients at least after 55 d (mean 73.21 d, SD = 19.16). All patients involved in the study were diagnosed in advanced tumor stages UICC III (n = 4; 6.8%), IVA (n = 27; 45.8%) and IVB (n = 28; 47.5%). Every patient was treated with curative neck dissection. Adjuvant chemo (immune) radiation was performed in 55 patients (93.2%), 4 patients (6.8%) underwent adjuvant radiation only. The mean follow-up time was 43.6 months (SD = 36.7 months). The 5-year OS rate for all patients involved was 71% (95% CI 0.55-0.86). For those patients receiving adjuvant therapy within 55 d (77, 95% CI 0.48-1.06) the OS rate was higher, yet not significantly different from those with delayed treatment (64, 95% CI 0.42-0.80; X2(1) = 1.16, p = 0.281). Regarding all patients, the 5-year DSS rate was 86% (95% CI 0.75-0.96). Patients submitted to adjuvant treatment in less than 55 d the DSS rate was 95% (95% CI 0.89-1.01) compared to patients submitted to adjuvant treatment equal or later than 55 d (76% (95% CI 0.57-0.95; X2(1) = 2.32, p = 0.128). The 5-year PFS rate of the entire cohort was 72% (95% CI 0.59-0.85). In the group < 55 d the PFS rate was 78% (95% CI 0.63-0.94) and thus not significantly different from 65% (95% CI 0.45-0.85) of the group ≥55 d; (X2(1) = 0.29, p = 0.589). CONCLUSIONS: The results presented suggest that the oncologic outcome of patients with advanced, HPV-negative CUP of the head and neck was not significantly affected by a prolonged period between surgery and adjuvant therapy. Nevertheless, oncologic outcome tends to be superior for early adjuvant therapy.

Is chemoimmunotherapy a game changer in the treatment of locally advanced head and neck squamous cell carcinoma?

Pembrolizumab and chemotherapy (chemoimmunotherapy) were administered to 2 head and neck squamous cell carcinoma (HNSCC) patients with extremely advanced local tumors and distant metastases with palliative intent. However, they demonstrated strikingly good responses and achieved remission. Expanded application of induction chemoimmunotherapy may be useful for locally advanced HNSCC.

Palliative Local Radiotherapy for Advanced Squamous Cell Carcinoma of the Head-and-Neck: Prognostic Factors of Survival.

BACKGROUND/AIM: A considerable number of patients with advanced head-and-neck cancer (SCCHN) receive palliative radiotherapy. This study aimed to identify prognostic factors for survival to facilitate personalized treatment for these patients. PATIENTS AND METHODS: Ninety-two patients receiving palliative radiotherapy for SCCHN were retrospectively analyzed. Fourteen characteristics were evaluated for survival including age, gender, performance score, pre-radiotherapy hemoglobin, tumor site and stage, histologic grade, p16-status, equivalent dose in 2 Gy-fractions (EQD2), completion of radiotherapy, upfront surgery and systemic therapy. RESULTS: On univariate analysis, improved survival was significantly associated with pre-radiotherapy hemoglobin ≥12 g/dl (p=0.003), EQD2 >42.3 Gy (p=0.003) and completion of radiotherapy (p<0.001). In the multivariate analysis, hemoglobin levels remained significant (p=0.024). Trends were found for EQD2 (p=0.057) and completion of radiotherapy (p=0.093). CONCLUSION: Prognostic factors for survival were identified that can facilitate treatment personalization. The fact that higher EQD2 and completion of radiotherapy were associated with improved survival demonstrates the importance of close monitoring and care of these patients during radiotherapy.

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.

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.

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.