Chemoradiotherapy For Squamous Cell Carcinoma Research Articles

Feasibility and safety of an active surveillance protocol after neoadjuvant chemoradiotherapy for squamous cell carcinoma of the esophagus.

Feasibility and safety of an active surveillance protocol after neoadjuvant chemoradiotherapy for squamous cell carcinoma of the esophagus.

Chemoradiotherapy for squamous cell carcinoma of the rectum: a retrospective propensity-score matched analysis

A lack of evidence-based data on the chemoradiotherapy (CRT) efficacy in patients with squamous cell carcinoma of the rectum (SCCR) makes further study of this topic extremely important.Aim: The aim of our research was to estimate the efficacy of CRT in patients with SCCR compared to the rectal adenocarcinoma and squamous cell carcinoma of the anal canal (SCCAC).Materials and methods: Our study was based on analysis of medical records of patients with ICD–X code C20 and ICD-O 8070 / 3, 8070 / 3.1, 80703 in a database from 2007 to 2020 obtained from the archive of Research Institute FSBI “N. N. Blokhin Cancer Research Center” of the Ministry of Health of Russia. We included patients with SCCR who received CRT as initial treatment into the experimental group. Groups with rectal adenocarcinoma and SCCAC were created using propensity-score matching 1:2 taking into account sex, age, the cN clinical stage, histological grade and tumor size. The main study endpoints were 3‑year overall survival (OS) and disease-free survival (DFS) rates, complete clinical response rate and complete clinical or pathological response rate at 6 months after CRT, local recurrence and distant metastases rates, surgery rate.Results: We included 15 patients in SCCR group and 30 patients in rectal adenocarcinoma group and SCCAC group each. There were no significant differences in parameters that could affect the prognosis. The complete clinical response was achieved in 7 (46.7 %) patients with SCCR versus 3 (10.0 %) patients with adenocarcinoma (p = 0.005) and 24 (80.0 %) patients with SCCAC (p = 0.005). The surgery rate was 26.6 % (4 patients) in SCCR group, 6.67 % (2 patients) in SCCAC group, 90 % (27 patients) in adenocarcinoma group (p < 0.001). The recurrence rate was 26.7 % (4 patients) in SCCR group versus 10.0 % (3 patients) in adenocarcinoma group (p = 0.146) and 6.7 % (2 patients) in SCCAC group (p = 0.063). The metastases rate was 26.7 % (4 patients) in SCCR group, 26.7 % (8 patients) in adenocarcinoma group (p > 0.99). In SCCAC group metastases were detected in 1 (3.3 %) patient, which was significantly different compared to the SCCR group (p = 0.019). Median follow up was 44 months. The 3‑year OS was 78.8 % in SCCR group versus 91.0 % in adenocarcinoma group (p = 0.675), and 86.3 % in SCCAC group (p = 0.953). The 3‑year OS in adenocarcinoma and SCCAC groups did not differ (p = 0.996). The 3‑year DFS was 34.7 % in SCCR group versus 55.6 % in adenocarcinoma group (p = 0.504) and 82.9 % in SCCAC group (p = 0.031). The 3‑year DFS differences in adenocarcinoma and SCCAC groups were significant (p = 0.041).Conclusions: We have obtained important data on the CRT comparative efficacy in patients with SCCR, SCCAC and rectal adenocarcinoma. The high complete clinical response rate in SCCR group makes it possible to consider the use of CRT as the main treatment method. Results of our research can be used to plan the treatment of patients with SCCR.

Survival outcomes following salvage abdominoperineal resection for recurrent and persistent anal squamous cell carcinoma

IntroductionThe primary treatment for locoregional failure following chemoradiotherapy for squamous cell carcinoma of the anus (SCCA) is salvage abdominoperineal resection (APR). However, it is necessary to distinguish between recurrent and persistent diseases because of their varied pathologies. We aimed to clarify the survival outcomes following salvage APR for recurrent and persistent diseases and investigate the significance of salvage APR. Materials and methodsThis multicentre retrospective cohort study used clinical data from 47 hospitals. All patients were diagnosed with SCCA and underwent definitive radiotherapy as the primary treatment between 1991 and 2015. Overall survival (OS) was compared between the following cohorts: salvage APR for recurrence, salvage APR for persistence, non-salvage APR for recurrence, and non-salvage APR for persistence. ResultsFive-year OS of salvage APR for recurrence, salvage APR for persistence, non-salvage APR for recurrence, and non-salvage APR for persistence were 75% (46%–90%), 36% (21%–51%), 42% (21%–61%), and 47% (33%–60%), respectively. OS of salvage APR for the recurrent disease was significantly higher than that for persistent disease (p = 0.00597). For recurrent disease, OS following salvage APR was significantly higher than that following non-salvage APR (p = 0.0204); however, for persistent disease, there was no significant difference between salvage and non-salvage APR (p = 0.928). ConclusionSurvival outcomes following salvage APR for persistent disease were significantly worse than that for recurrent disease. Salvage APR did not improve survival outcomes for persistent disease compared to non-salvage APR. These results will elicit a review of persistent disease treatment strategies.

Concurrent Chemoradiotherapy in Squamous Cell Carcinoma of the Anal Canal: A Tertiary Care Experience in North India

ABSTRACT Aim: The aim of this study was to study the treatment outcome and survival of squamous cell carcinoma anal canal using concurrent chemoradiotherapy in a tertiary care hospital. Materials and Methods: This was a retrospective study performed in our hospital, in which all necessary clinical and epidemiological details of the 38 cases diagnosed with squamous cell carcinoma anal canal from January 2015 to December 2021 were analyzed. Results: Most patients were male in gender, 22 (57.90%) and 16 (42.10%) were females, with a male: female ratio of (1.37:1). All patients received concurrent chemoradiation as the definitive treatment. The mean 5-year survivals were (48 months). Five years of overall survival was 68% and for clinical stage I, II, and III was 100%, 64%, and 37%, respectively. Conclusion: The standard of care for stage I to III anal squamous cell carcinoma is concurrent chemoradiotherapy with 5-fluorouracil and mitomycin-C with excellent response rates.

Outcome of Chemoradiotherapy for Squamous Cell Carcinoma of the Anorectal Region

Outcome of Chemoradiotherapy for Squamous Cell Carcinoma of the Anorectal Region

One-Year Treatment-Related Side Effects and Quality of Life After Chemoradiotherapy in Squamous Cell Carcinoma of the Anus

Patient-reported outcome (PRO) and National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) data for patients with squamous cell carcinoma of the anus (SCCA) treated with modern radiation therapy (RT) are lacking. The primary aim of this study was to report bowel and bladder PRO and NCI-CTCAE for patients with SCCA 1 year after RT. From 2015 to 2020, we included patients in a prospective Danish national study. Data were collected before treatment (PT) and 1 year after treatment (1Y) using NCI-CTCAE version 4.0, as well as European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and CR29. We evaluated the combined PRO scores according to the European Organisation for Research and Treatment of Cancer scoring guidelines, and classified changes according to score difference from PT to 1Y as no change (0-5), minor (5-10), moderate (11-20), and major (>20). Raw scores were reported as frequencies of each of the scores: Not at all, a little, quite a bit, and very much. Of the 270 patients, 81% had complete data sets, including PT and 1Y answers. Functional mean scores were equal to a matched normal population cohort at PT and 1Y. From PT to 1Y, C30 scores were stable despite minor improvements in global health status/quality of life (7.3), emotional functioning (9.3), insomnia (8.0), and appetite loss (7.8). For questionnaire CR29, bowel and bladder symptoms and sore skin improved with minor change (6.2), and buttocks, anal, or rectal pain improved with moderate change (18.3). Flatulence worsened moderately (12.6), and fecal incontinence had minor worsening (7.8). Agreement between PROs and NCI-CTCAE was generally only fair to moderate, especially for quantitative symptoms, such as pain (κ=0.25). For patients with SCCA who underwent definitive RT, only a few patients had high scores (indicating quite a bit or very much frequency of bother) regarding bowel and bladder symptoms.

Predicting treatment response to concurrent chemoradiotherapy in squamous cell carcinoma of the cervix using amide proton transfer imaging and intravoxel incoherent motion imaging

PurposeThe purpose of this study was to investigate whether amide proton transfer (APT) imaging and intravoxel incoherent motion (IVIM) imaging can predict tumor response to concurrent chemoradiotherapy (CCRT) in patients with squamous cell carcinoma of the cervix (SCCC). Material and methodsFifty-nine women (mean age, 54 years ± 10 [standard deviation] years; age range: 32−81 years) with pathologically confirmed SCCC underwent magnetic resonance imaging examination of the pelvis including APT and IVIM before concurrent chemoradiotherapy. They were divided into complete remission (CR) and non-CR groups according to therapeutic effect. APT values and IVIM-derived parameters were measured. Intra- and interobserver agreement for IVIM and APT parameters was assessed using intraclass correlation coefficient (ICC) The independent samples t-test was performed to compare the evaluated parameters between the two groups. Predictive performance for treatment response was evaluated by receiver operator characteristic (ROC) curve analysis. ResultsThere were 38 and 21 patients in the non-CR and CR groups, respectively. Excellent interobserver and intraobserver agreement were obtained for all IVIM and APT parameters, with ICCs ranging from 0.844 to 0.962. Perfusion fraction (f) and APT values were lower in the CR group compared with the non-CR group (both P < 0.05). The combination of f and APT values showed good diagnostic performances in predicting response to concurrent chemoradiotherapy, with an area under the ROC curve of 0.852 (95% CI: 0.744–0.961), 79% sensitivity (95% CI: 63–90%), 90% specificity (95% CI: 70–99%) and 83% accuracy (95% CI: 71–92%). ConclusionAPT and IVIM imaging may serve as noninvasive tools for predicting response to concurrent chemoradiotherapy in patients with SCCC.

Mesorectal failure after chemoradiotherapy for squamous cell carcinoma of the anus: is sphincter-saving surgery reasonable?

Abdominoperineal resection (APR) is today the standard treatment for improving survival in case of mesorectal failure without anal canal recurrence after chemoradiotherapy (CRT) for squamous cell carcinoma of the anus (SCC). The aim of this study was to assess if a sphincter-saving surgery is a safe alternative to classical salvage APR in these patients. A retrospective study was conducted on all patients who had total mesorectal excision (TME) with sphincter-saving surgery either with coloanal or low colorectal anastomosis, for mesorectal failure after CRT for SCC between 2012 and 2020 at our institution. The main endpoint of our study was oncological results at the end of follow-up. Postoperative morbidity and mortality were secondary endpoints. There were 10 patients, (8 women, median age 55years [range 45-61years]). On TME specimens, R0 resections were noted in five (50%), R1 resection in four (40%) and R2 resection in one (10%). After a median follow-up of 42months (4-74months), five patients were alive, and four (40%) were alive at 5-year follow-up. During follow-up, locoregional failure after TME was noted in two patients (20%), distant relapse in three patients (30%) and both locoregional plus distant failure in two patients (20%). Only two patients (20%) had anal recurrence, one in the anal canal, the other in the peri-anastomotic area. Long- term local control was achieved in 2 of the 5 patients (40%) who underwent R0 resection versus only 1/4 patients (25%) with R1 resection. Our preliminary study suggested that sphincter-saving surgery could be proposed in selected patients with SCC presenting mesorectal failure after CRT, providing a feasible R0 resection.

Short- and Long-term Outcomes of Chemoradiotherapy for Squamous Cell Carcinoma of the Anal Canal in 17 Patients

欧米では肛門管扁平上皮癌に対する標準治療は化学放射線療法（CRT）とされているが，本邦ではCRTの治療成績についての報告は少ない．当科では2008年1月からCRTを標準療法としており，2019年2月までに肛門管扁平上皮癌と診断した17例に対するCRTの短期・長期治療成績を検討した．Grade3以上の有害事象は，骨髄抑制（47.1％），下痢（5.9％），放射線性皮膚炎（53.0％）であった．13例は無再発であったが4例で局所再発を認めた．4例中3例にはサルベージ手術を1例には組織内照射を行い，2例は現在も無再発生存中である．局所再発を認めた2例はヒト免疫不全ウイルス（HIV）感染を合併しており，ともに予後不良であった．3年無病生存率は76.5％，3年全生存率は88.2％であった．肛門管扁平上皮癌に対するCRTは安全に施行可能であり，長期成績についても認容される結果であることが示唆された．

Spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis: a case report

BackgroundSpindle cell squamous cell carcinoma is an uncommon variant of squamous cell carcinoma; its diagnosis is sometimes challenging because it histopathologically resembles neoplastic or reactive spindle cell lesions of mesenchymal origins. Here, we report a rare case of spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis.Case presentationA 69-year-old Japanese man presented with pain and a polypoid mass on the lower left gingiva. He had received chemoradiotherapy for squamous cell carcinoma of the buccal mucosa 15 years prior to this consultation. In addition, he was treated for mandibular osteonecrosis 6 years after chemoradiotherapy without evidence of cancer recurrence. A biopsy revealed atypical spindle or pleomorphic cells scattered in the edematous and fibrin-rich stroma; however, no malignant squamous components were apparent. These atypical cells frequently contained neutrophils within their cytoplasm that formed cell-in-cell figures. Immunohistochemically, the atypical cells were negative for cytokeratins, epithelial membrane antigen, and E-cadherin, but positive for p63, vimentin, and p53. Although these findings suggested spindle cell squamous cell carcinoma, it was difficult to reach a definitive diagnosis. Based on a clinical diagnosis of a malignant tumor, the patient underwent a hemimandibulectomy. The surgically resected specimen had a typical spindle cell squamous cell carcinoma histology consisting of biphasic spindle cells and conventional squamous cell carcinoma components. Moreover, the surgical specimen also exhibited spindle tumor cells that frequently included neutrophils, around which intense staining for lysosomal-associated membrane protein 1 and cathepsin B was observed. This suggested that the cell-in-cell figures represent active neutrophil phagocytosis by tumor cells, and not emperipolesis.ConclusionThe presence of neutrophil phagocytosis may be a potent indicator of malignancy.

Trimodality Versus Bimodality Therapy in Patients With Locally Advanced Esophageal Carcinoma: Commentary on the American Society of Clinical Oncology Practice Guidelines

In the recent guideline statement from the American Society of Clinical Oncology, experts reviewed relevant literature and provided treatment recommendations for multimodality treatment approaches. The guidelines recommend either preoperative concurrent neoadjuvant chemoradiotherapy (CRT) or perioperative chemotherapy for locally advanced adenocarcinoma and either preoperative CRT followed by esophagectomy or definitive CRT for squamous cell carcinoma. Whether radiation can be omitted in patients with adenocarcinoma or whether surgery can be omitted in patients with squamous cell carcinoma is a subject of ongoing debate and clinical trials.

Definitive chemoradiotherapy for squamous cell carcinoma of the anal canal (SCCAC) with cisplatin and capecitabine: A prospective cohort—preliminary results.

e15506 Background: SCCAC is a rare disease. The standard care treatment with curative intent is chemoradiation with mitomycin (MMC) or cisplatin (CDDP) plus infusional 5-FU. Capecitabine may replace 5-FU in MMC doublet. However, MMC and infusional pumps are unavailable in many underdeveloped countries, and there is a lack of prospective data regarding the feasibility and safety of capecitabine combined with CDDP in definitive chemoradiotherapy. Methods: A Prospective cohort study aimed to evaluate the safety and efficacy of treatment with chemoradiation with CDDP60mg/m2 D1 and D29 plus capecitabine 825mg/m2/day BID in a population without MMC and infusional pump access. Eligible pts had T2-4/N0-3/M0 disease and were candidates to full curative CRT. Toxicity evaluation was the primary endpoint, secondary endpoint was response by RECIST v.1.1 at 8 weeks(w) and 6 months(m). The study data were prospectively collected using REDCap. Results: 23 pts were enrolled from Aug/2019 to Oct/2020 with a median follow-up of 7m. Median age 59 years; 76% (n=16) were stage III, 48% (n=11) were ECOG1, and 15% (n=3) were HIV+. All pts received concomitant radiotherapy, MVAT, with a median dose 54Gy in the primary tumor and 45Gy in elective nodes. At 8w, 18 patients were evaluable for response, 56% (n=10) had complete response (CR),39% (n=7) had partial response (PR) and 5% (n=1) progressive disease (PD). At 6 months 11 patients were evaluable for response, 64%(n=7) had CR, 18% (n=2) PR and 18% (n=2) PD. Any grade 3/4 toxicity was present in six pts, four of them radiodermatitis. The most frequent grade toxicities were nausea and radiodermatitis in all pts, anemia 81% (n=17), diarrhea 62% (n=13). Two older pts had definitive suspension of treatment due to toxicity. Three pts had hospitalization because of a skin infection. Six pts had disease recurrence, and two died by the cutoff date. One death related to diarrhea and vomiting toxicity in an older 84-year pt. OS and PFS are not reached. Conclusions: Definitive chemoradiotherapy with cisplatin and capecitabine is feasible; however, the older population is more vulnerable to treatment complications. Further prospective studies with a higher number of patients and longer follow up are required to evaluate SLP and OS.

The Clinical Value of Measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus

Simple SummaryAnal cancer is treated with high dose chemoradiotherapy; but despite this, a minor patient group experience treatment failure. Anal cancer is strongly related to human papilloma virus (HPV) infection and previous smaller studies have shown that fragments of HPV DNA can be detected in blood samples from anal cancer patients. This study measured HPV DNA in 88 patients including both small- and more advanced tumors and detected six different subtypes of HPV. During treatment with chemoradiotherapy, the level of HPV DNA decreased, and three elimination patterns with clinical relevance were identified. Fast elimination correlated to a low risk of failure, slow elimination correlated to risk of failure in the pelvis, and persistent HPV DNA after treatment correlated to a high risk of later distant failure. The results add new information to the increasing interest in research of HPV DNA in HPV related cancers and holds great clinical potential.Background and purpose: Circulating tumor DNA (ctDNA) is investigated in various cancers. In squamous cell carcinoma of the anus (SCCA) infection with human papilloma virus (HPV) is found in around 90% of cases and here, plasma HPV (pHPV) can be used as ctDNA. Preliminary data have proved the ability to detect pHPV16 and -18 in SCCA. We have developed a highly sensitive method for measurement of six relevant pHPV subtypes, to investigate the elimination pattern of pHPV during chemo-radiotherapy (CRT) for SCCA and its clinical value. Material and methods: Patients treated at Aarhus University Hospital from 2016–2020 were included. P16 status in the primary biopsy was measured and 82% of patients had P16 positive tumor. Blood samples were collected prior to treatment (PT), mid treatment (MT), end of therapy (EOT), and during follow-up (FU). An in-house multiplex digital droplet PCR method measured pHPV subtypes 16, 18, 31, 33, 51, 58. Results: Samples from 88 patients were drawn PT (n = 73), MT (n = 72), EOT (n = 64) and during FU (n = 41). Plasma HPV was detectable in 52 patients and PT pHPV levels correlated to tumor stages. Three elimination patterns were observed during CRT with correlation to outcome: fast responders with no local or distant failures (0/12); slow responders with high risk of local failures (4/20), no distant failures; persistent molecular responders with high risk of distant failures (4/13), but no local failures, p < 0.01. Conclusion: During CRT, pHPV can divide patients with SCCA into three groups with significantly different risk of failure. The use of pHPV can potentially assist in clinical treatment decision.

Three-dimensional (3D) magnetic resonance volume assessment and loco-regional failure in anal cancer: early evaluation case-control study

BackgroundThe primary aim was to test the hypothesis that deriving pre-treatment 3D magnetic resonance tumour volume (mrTV) quantification improves performance characteristics for the prediction of loco-regional failure compared with standard maximal tumour diameter (1D) assessment in patients with squamous cell carcinoma of the anus undergoing chemoradiotherapy.MethodsWe performed an early evaluation case-control study at two UK centres (2007–2014) in 39 patients with loco-regional failure (cases), and 41 patients disease-free at 3 years (controls). mrTV was determined using the summation of areas method (Volsum). Reproducibility was assessed using intraclass concordance correlation (ICC) and Bland-Altman limits of agreements. We derived receiver operating curves using logistic regression models and expressed accuracy as area under the curve (ROCAUC).ResultsThe median time per patient for Volsum quantification was 7.00 (inter-quartile range, IQR: 0.57–12.48) minutes. Intra and inter-observer reproducibilities were generally good (ICCs from 0.79 to 0.89) but with wide limits of agreement (intra-observer: − 28 to 31%; inter-observer: − 28 to 46%). Median mrTVs were greater for cases (32.6 IQR: 21.5–53.1 cm3) than controls (9.9 IQR: 5.7–18.1 cm3, p < 0.0001). The ROCAUC for mrT-size predicting loco-regional failure was 0.74 (95% CI: 0.63–0.85) improving to 0.82 (95% CI: 0.72–0.92) when replaced with mrTV (test for ROC differences, p = 0.024).ConclusionPreliminary results suggest that the replacement of mrTV for mrT-size improves prediction of loco-regional failure after chemoradiotherapy for squamous cell carcinoma of the anus. However, mrTV calculation is time consuming and variation in its reproducibility are drawbacks with the current technology.

PET Radiomics Analysis for Prediction of Metabolic Complete Response of Primary Tumor After Chemo-Radiotherapy for Squamous Cell Carcinoma of Cervix Uteri

PET Radiomics Analysis for Prediction of Metabolic Complete Response of Primary Tumor After Chemo-Radiotherapy for Squamous Cell Carcinoma of Cervix Uteri

Haematotoxicity in IMRT/VMAT curatively treated anal cancer.

Curative chemoradiotherapy of squamous cell carcinoma achieves long-term complete remissions in most patients and minimizing treatment toxicity becomes crucial issue. The aim of the retrospective analysis was to determine an acceptable dose to the bone marrow for radiotherapy planning not leading to increased haematological toxicity. In the period 2013-2019, 40 patients with squamous cell carcinoma were curatively treated at the Department of Oncology of the University Hospital Motol using intensity modulated radiotherapy (IMRT) /volumetric modulated arc radiotherapy (VMAT) technique. Women make up 90% of the group, the average age at the time of dia-gnosis was 65 years (47-81). Chemotherapy mitomycin C and 5-fluorouracil was given to 68% of patients. The bone marrow was contoured in the Varian Eclipse planning system, version 15.6. Acute hematotoxicity (G3, 4, 5 according to Common Terminology Criteria for Adverse Events - CTCAE) was significantly associated with the concomitant chemoradiotherapy (P = 0.002) and the average dose to the bone marrow 27 Gy (P = 0.011). Late haematological toxicity was mild (maximum grade 1), asymptomatic, and no dependence of late haematotoxicity on any risk factor (age, gender, WHO performance status, bone marrow dose, CHT, BMI, smoking, stage) was proved. The overall survival at 5 years was 100% in stage I, 83% in stage II, 61% in stage III and 0% in stage IV. Local control at 5 years is 100% in stage I, 92% in stage II, 87% in stage III and 0% in stage IV. Local recurrence developed in 5% of radically treated patients. Distant metastases occurred in 8% of radically treated patients. Local recurrences or metastases occurred only during the first 2 years after the treatment. Radical chemoradiotherapy in the treatment of squamous cell anal carcinoma is highly effective. IMRT/VMAT enabled to apply a sufficiently effective dose to the tumor and elective areas and reduced not only acute skin, GI and GU toxicity, but also acute haematological toxicity in cases with the dose Dmean to bone marrow lower than 27 Gy. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical, papers.

Phase III Randomized Study of Induction Chemotherapy Followed by Definitive Radiotherapy + Cetuximab Versus Chemoradiotherapy in Squamous Cell Carcinoma of Head and Neck: The INTERCEPTOR-GONO Study (NCT00999700)

Objectives: Induction chemotherapy followed by cetuximab and RT (IBRT) (Arm A) was compared to cisplatin/RT (CRT) (Arm B) in a randomized phase III study. Patients and Methods: Naïve patients with stage III-IVa, histologically proven locally advanced head and neck cancer (LASCCHN) were eligible. Arm A (IBRT): 3 TPF induction followed by cetuximab-RT (equivalent daily dose 2 Gy up to 70 Gy); Arm B: 3 cisplatin concurrent with the same RT scheduling. Due to slow accrual and incomplete data collection a futility analysis was performed. Results: 236/282 patients were evaluable. Therefore, no formal analyses can be made between the two arms. OS was 45.2/53.6 months in Arm A/B. Complete responses were achieved in 64% of patients in both arms. Neutropenia and skin toxicity were significantly worse in Arm A and body weight loss was significantly worse in Arm B. Compliance with the planned drug administration was higher in Arm B (p = 0.0008). Conclusion: The study suggests that IBRT and CRT have similar efficacy, activity and toxicity.

Treatment implications of postoperative chemoradiotherapy for squamous cell carcinoma of the oral cavity with minor and major extranodal extension.

To evaluate adjuvant chemoradiotherapy (CRT) for patients with oral cavity squamous cell carcinoma (OSCC) with minor or major extranodal extension (ENE). Surgically resected OSCC with pathologically involved lymph node(s) (pN+) between 2006 and 2017. Sections of pN+ were re-reviewed and classified as no, minor (≤2 mm), or major (>2 mm) ENE. Patterns of failure and survival were compared between the groups and stratified by adjuvant treatment. Multivariable (MVA) analysis assessed the value of adjuvant treatment for minor and major ENE. Total of 384 patients, 62 had minor and 114 had major ENE. Adjuvant CRT was delivered in 32(15%), 21(34%), and 45(39%) of patients with no, minor and major ENE, respectively. Patients with minor ENE had similar 5-year loco-regional control (LRC) and distant control (DC) but lower disease-free survival (DFS) (38% vs. 51%, p=0·02) compared to patients with no ENE, while patients with major ENE had marginally lower LRC (59% vs 74%, p=0·07), lower DC (58% vs 82%,p=0·005) and DFS (13% vs. 38%, p=·001) compared to those with minor. On MVA, adjuvant chemotherapy was associated with improved DFS for major ENE (adjusted HR=0·49; 95% CI 0·29-0·85, p=0·01) but not for minor ENE after adjusting for age, ECOG status, T-, N-category, margin status, and radiotherapy. Adjuvant chemoradiotherapy improves outcomes in patients with major ENE, but the benefit is unclear in patients with minor ENE. Future trials should focus on intensification of treatment for patients with major ENE and alternative adjuvant strategies for patients with minor ENE.

Definitive chemoradiotherapy for squamous cell carcinoma of the esophagus: outcomes for borderline-resectable disease.

Definitive chemoradiotherapy (dCRT) is the standard treatment for unresectable esophageal cancer. Induction chemotherapy has been actively investigated for borderline-resectable and unresectable disease, but the superiority over dCRT has yet to be confirmed. The purpose of this study was to evaluate the outcome of dCRT with special interest in borderline-resectable disease. Patients with esophageal cancer treated with dCRT between January 2004 and November 2016 were included in this retrospective analysis. Chemotherapy consisted of two cycles of cisplatin (70–75 mg/m2) on day 1 and 5-fluorouracil (700–1000 mg/m2 per day) on days 1–4 or low-dose cisplatin (10 mg/m2 per day) and 5-fluorouracil (175 mg/m2 per day) for 20 days. Radiotherapy was given with a daily fraction of 1.8–2 Gy to a total dose of 50–70 Gy. A total of 104 patients were included: 34 were resectable, 35 were borderline-resectable and 35 were unresectable. Complete response was achieved in 44 patients (42%). Eighteen patients (17%) suffered Grade 2 or greater cardiopulmonary toxicity and seven patients (7%) suffered Grade 3 cardiopulmonary toxicity. At the time of this analysis, 59 patients were dead and 45 were censored. The 3-year overall survival proportions for resectable, borderline-resectable and unresectable patients were 64%, 46% and 21%, respectively. The overall survival for borderline-resectable patients with complete response and noncomplete response was significantly different (P < 0.001), with 3-year survival of 70% and 8%, respectively. The overall survival for complete response patients with borderline-resectable disease was encouraging. Further investigation to find a subgroup fit for esophagus-preserving treatment is warranted.

Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck

Locoregionally advanced head and neck squamous cell cancer (HNSCC) is treated curatively; however, risk of recurrence remains high among some patients. The ERBB family blocker afatinib has shown efficacy in recurrent or metastatic HNSCC. To assess whether afatinib therapy after definitive chemoradiotherapy (CRT) improves disease-free survival (DFS) in patients with HNSCC. This multicenter, phase 3, double-blind randomized clinical trial (LUX-Head & Neck 2) studied 617 patients from November 2, 2011, to July 4, 2016. Patients who had complete response after CRT, comprising radiotherapy with cisplatin or carboplatin, with or without resection of residual disease, for locoregionally advanced high- or intermediate-risk HNSCC of the oral cavity, hypopharynx, larynx, or oropharynx were included in the study. Data analysis was of the intention-to-treat population. Patients were randomized (2:1) to treatment with afatinib (40 mg/d) or placebo, stratified by nodal status (N0-2a or N2b-3) and Eastern Cooperative Oncology Group performance status (0 or 1). Treatment continued for 18 months or until disease recurrence, unacceptable adverse events, or patient withdrawal. The primary end point was DFS, defined as time from the date of randomization to the date of tumor recurrence or secondary primary tumor or death from any cause. Secondary end points were DFS at 2 years, overall survival (defined as time from the date of randomization to death), and health-related quality of life. A total of 617 patients were studied (mean [SD] age, 58 [8.4] years; 528 male [85.6%]). Recruitment was stopped after a preplanned interim futility analysis on July 4, 2016, on recommendation from an independent data monitoring committee. Treatment was discontinued. Median DFS was 43.4 months (95% CI, 37.4 months to not estimable) in the afatinib group and not estimable (95% CI, 40.1 months to not estimable) in the placebo group (hazard ratio, 1.13; 95% CI, 0.81-1.57; stratified log-rank test P = .48). The most common grade 3 and 4 drug-related adverse effects were acneiform rash (61 [14.8%] of 411 patients in the afatinib group vs 1 [0.5%] of 206 patients in the placebo group), stomatitis (55 [13.4%] in the afatinib group vs 1 [0.5%] in the placebo group), and diarrhea (32 [7.8%] in the afatinib group vs 1 [0.5%] in the placebo group). This study's findings indicate that treatment with afatinib after CRT did not improve DFS and was associated with more adverse events than placebo in patients with primary, unresected, clinically high- to intermediate-risk HNSCC. The use of adjuvant afatinib after CRT is not recommended. ClinicalTrials.gov identifier: NCT01345669.