Adjuvant chemotherapy after radiotherapy or concurrent chemoradiotherapy for pelvic lymph node-positive patients with locally advanced cervical cancer: a propensity score matching analysis.

OBJECTIVE: The benefit of adjuvant chemotherapy after definitive chemoradiotherapy in patients with pelvic lymph node-positive cervical cancer has been poorly studied. This study aimed to test the hypothesis that the addition of adjuvant chemotherapy to definitive radiotherapy or concurrent chemoradiotherapy improves survival in patients with pelvic lymph node-positive cervical squamous cell carcinoma. METHODS: This retrospective study enrolled patients with stage IB-IVA pelvic lymph node-positive cervical squamous cell carcinoma, without para-aortic lymph node metastases and initially treated with definitive radiotherapy or concurrent chemoradiotherapy between March 2007 and February 2018. Patients were classified into the adjuvant chemotherapy (5-fluorouracil or paclitaxel, plus cisplatin) and no-adjuvant chemotherapy groups. Treatment outcomes were compared between the two groups before and after 1:1 ratio propensity score matching. RESULTS: Medical records of 951 patients were reviewed and 792 patients were excluded. Finally, 159 patients were enrolled for analysis. Of these, 42 patients received a median of two cycles (range, 1-6) of adjuvant chemotherapy and 117 patients under observation after primary treatment. The median follow-up period was 33.8 months (range, 2.9-113.0). Before propensity score matching, no significant difference was observed in survivals between the two groups (P>0.05). After propensity score matching, 37 pairs of patients were selected. The 3-year rates of progression-free survival, overall survival, local control, and distant metastasis-free survival in the adjuvant chemotherapy and no-adjuvant chemotherapy groups were 80.2% and 60.4% (P=0.07), 83.0% and 63.7% (P=0.17), 94.0% and 81.9% (P=0.12), and 85.9% and 60.1% (P=0.04), respectively. The incidences of grade 3-4 acute and late toxicities were comparable between the two groups (P>0.05). DISCUSSION: Adjuvant chemotherapy significantly improved 3-year distant metastasis-free survival in patients with pelvic lymph node-positive cervical squamous cell carcinoma. Further prospective studies are needed to provide supportive evidence for the therapeutic efficacy of adjuvant chemotherapy.

Factors associated with under-reporting of head and neck squamous cell carcinoma in cause-of-death records: A comparative study of two national databases in France from 2008 to 2012.

OBJECTIVE: To date, no study has evaluated the detection rate of head and neck squamous cell carcinoma (HNSCC) in cause-of-death records in Europe. Our objectives were to compare the number of deaths attributable to HNSCC from two national databases in France and to identify factors associated with under-reporting of HNSCC in cause-of-death records. METHODS: The national hospital discharge database and the national underlying cause-of-death records were compared for all HNSCC-attributable deaths in adult patients from 2008 to 2012 in France. Factors associated with under-reporting of HNSCC in cause-of-death records were assessed using multivariate Poisson regression. RESULTS: A total of 41,503 in-hospital deaths were attributable to HNSCC as compared to 25,647 deaths reported in national UCoD records (a detection rate of 62%). Demographics at death were similar in both databases with respect to gender (83% men), age (54% premature deaths at 25-64 years), and geographic distribution. In multivariate Poisson regression, under-reporting of HNSCC in cause-of-death records significantly increased in 2012 compared to 2010 (+7%) and was independently associated with a primary HNSCC site other than the larynx, a former primary or second synchronous cancer other than HNSCC, distant metastasis, palliative care, and death in hospitals other than comprehensive cancer care centers. The main study results were robust in a sensitivity analysis which also took into account deaths outside hospital (overall, 51,129 HNSCC-attributable deaths; a detection rate of 50%). For the year 2012, the age-standardized mortality rate for HNSCC derived from underlying cause-of-death records was less than half that derived from hospital discharge summaries (14.7 compared to 34.1 per 100,000 for men and 2.7 compared to 6.2 per 100,000 for women). CONCLUSION: HNSCC is largely under-reported in cause-of-death records. This study documents the value of national hospital discharge databases as a complement to death certificates for ascertaining cancer deaths.

Optimal Radiotherapy Dose in Anal Cancer: Trends in Prescription Dose and Association with Survival.

PURPOSE: Definitive chemoradiotherapy represents a standard of care treatment for localized anal cancer. National Comprehensive Cancer Network guidelines recommend radiotherapy (RT) doses of ≥ 45 Gy and escalation to 50.4-59 Gy for advanced disease. Per RTOG 0529, 50.4 Gy was prescribed for early-stage disease (cT1-2N0), and 54 Gy for locally advanced cancers (cT3-T4 and/or node positive). We assessed patterns of care and overall survival (OS) with respect to the RT dose. METHODS: The National Cancer Database identified patients with non-metastatic anal squamous cell carcinoma from 2004 to 2015 treated with chemoradiotherapy. Patients were stratified by RT dose: 40-< 45, 45-< 50, 50-54, and > 54-60 Gy. Crude and adjusted hazard ratios (HR) were computed using Cox regression modeling. RESULTS: A total of 10,524 patients were identified with a median follow-up of 40.7 months. The most commonly prescribed RT dose was 54 Gy. On multivariate analysis, RT doses of 40-< 45 Gy were associated with worse OS vs. 50-54 Gy (HR 1.68 [1.40-2.03], P < 0.0001). There was no significant difference in OS for patients who received 45-< 50 or > 54-60 Gy compared with 50-54 Gy. For early-stage disease, there was no significant association between RT dose and OS. For locally advanced disease, 45-< 54 Gy was associated with worse survival vs. 54 Gy (HR 1.18 [1.04-1.34], P = 0.009), but no significant difference was detected comparing > 54-60 Gy vs. 54 Gy (HR 1.08 [0.97-1.22], P = 0.166). CONCLUSIONS: For patients with localized anal cancer, RT doses of ≥ 45 Gy were associated with improved OS. For locally advanced disease, 54 Gy but not > 54 Gy was associated with improved OS.

Comparative effectiveness trial of transoral head and neck surgery followed by adjuvant radio(chemo)therapy versus primary radiochemotherapy for oropharyngeal cancer (TopROC).

BACKGROUND: For loco-regionally advanced, but transorally resectable oropharyngeal cancer (OPSCC), the current standard of care includes surgical resection and risk-adapted adjuvant (chemo) radiotherapy, or definite chemoradiation with or without salvage surgery. While transoral surgery for OPSCC has increased over the last decade for example in the United States due to transoral robotic surgery, this treatment approach has a long history in Germany. In contrast to Anglo-Saxon countries, transoral surgical approaches have been used frequently in Germany to treat patients with oro-, hypopharyngeal and laryngeal cancer. Transoral laser microsurgery (TLM) has had a long tradition since its introduction in the early 70s. To date, the different therapeutic approaches to transorally resectable OPSCC have not been directly compared to each other in a randomized trial concerning disease control and survival. The goal of this study is to compare initial transoral surgery to definitive chemoradiation for resectable OPSCC, especially with regards to local and regional control. METHODS: TopROC is a prospective, two-arm, open label, multicenter, randomized, and controlled comparative effectiveness study. Eligible patients are ≥18 years old with treatment-naïve, histologically proven OPSCC (T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0 UICC vers. 7) which are amenable to transoral resection. Two hundred eighty patients will be randomly assigned (1:1) to surgical treatment (arm A) or chemoradiation (arm B). Standard of care treatment will be performed according to daily routine practice. Arm A consists of transoral surgical resection with neck dissection followed by risk-adapted adjuvant therapy. Patients treated in arm B receive standard chemoradiation, residual tumor may be subject to salvage surgery. Follow-up visits for 3 years are planned. Primary endpoint is time to local or locoregional failure (LRF). Secondary endpoints include overall and disease free survival, toxicity, and patient reported outcomes. Approximately 20 centers will be involved in Germany. This trial is supported by the German Cancer Aid and accompanied by a scientific support program. DISCUSSION: This study will shed light on an urgently-needed randomized comparison of the strategy of primary chemoradiation vs. primary surgical approach. As a comparative effectiveness trial, it is designed to provide data based on two established regimens in daily clinical routine. TRIAL REGISTRATION: NCT03691441 Registered 1 October 2018 - Retrospectively registered.

USP9X mRNA expression predicts clinical outcome for esophageal squamous cell carcinoma treated with cisplatin-based therapy.

INTRODUCTION: Combination therapy with cisplatin is the conventional first-line treatment in patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). Ubiquitin-specific protease 9X (USP9X) has been shown to be associated with resistance to chemotherapy drugs in several cancers. The purpose of this study was to explore the predictive effects of USP9X on advanced ESCC patients treated with cisplatin-based regimens. MATERIALS AND METHODS: The subjects were 69 advanced ESCC patients who received first-line cisplatin-based chemotherapy or chemoradiotherapy. The quantitative real-time PCR was performed to measure USP9X mRNA expression. The correlation of USP9X expression with clinical parameters and tumor response was analyzed. The Kaplan-Meier method and Cox analysis were employed to analyze differences in overall survival (OS). RESULTS: USP9X mRNA expression was positively associated with the TMN stage at initial diagnosis. Patients with low USP9X mRNA expression had a significantly higher objective response rate (57.1% vs. 17.6%, P=0.001) and longer median OS (25.0 vs. 14.0 months, P<0.001) than those with high expression in all patients or in different treatment subgroups (all P<0.05). Multivariate analysis showed that low mRNA expression of USP9X emerged as an independent prognostic factor indicating prolonged OS (hazard ratio 0.50, 95% CI 0.34-0.73; P<0.001). CONCLUSION: These findings suggest that high USP9X mRNA expression predicts poor clinical efficacy and survival to cisplatin-based therapy in patients with advanced ESCC.

Increased High-Risk Human Papillomavirus Viral Load Is Associated With Immunosuppressed Microenvironment and Predicts a Worse Long-Term Survival in Cervical Cancer Patients.

OBJECTIVES: To evaluate the correlation between tumor-infiltrating lymphocytes (TILs) and the viral load of high-risk human papillomavirus (HR-HPV) in cervical cancer patients. METHODS: A total of 62 cervical cancer patients were recruited during 1993-1994 and assigned into four groups treated with radiotherapy alone or radiotherapy combined with chemotherapy and/or thermotherapy. Ki67+ tumor cells, CD4+, CD8+, FoxP3+, OX40+ and granzyme B+ TILs were detected by immunohistochemistry. The viral load of HR-HPV in biopsy tissues before therapy was detected by in situ hybridization. RESULTS: The patients with high HPV viral load showed a significantly lower 15-year survival rate and an advanced International Federation of Gynecology and Obstetrics (FIGO) stage and increased recurrence rate. The distribution of Ki67+ tumor cells, FoxP3+ TILs, and CD8+/FoxP3+ ratio was obviously different between low and high HPV viral load groups. A worse clinical outcome was also implicated with increased HPV viral load tested by Cox regression analysis. CONCLUSIONS: Patients with increased HR-HPV viral load tend to be resistant to therapy with decreased immune surveillance in the immune microenvironment. Thus, HR-HPV viral load would influence the local immune microenvironment, and then further affect the survival of cervical cancer patients.

Amino acids signatures of distance-related surgical margins of oral squamous cell carcinoma.

BACKGROUND: Histological assessment of resected margins has some drawbacks. We therefore aimed to identify a panel of metabolic markers for evaluating the surgical margins of oral squamous cell carcinoma during surgery. METHODS: A total of 28 case of OSCC samples were enrolled in the study. Gas chromatography-mass spectrometry based untargeted metabolic analysis was employed to acquire the metabolic perturbation of the distance-related surgical margins in the development group. The acquired MS data were then subjected to univariate and multivariate analysis by MetaboAnalyst. Ultra-high performance liquid chromatography-tandem mass spectrometerbased targeted metabolomics for quantitative analysis of the validation group was performed to verify the results of the development group. Another 60 OSCC patients with dysplastic surgical margins were used to further validate the results of the development group by immunohistochemical examination of key enzyme expression, and correlate them with clinicopathological parameters and clinical outcomes. FINDINGS: We finally identified 4 amino acids as negative margin markers, and 6 amino acids as dysplastic margin markers. IHC analysis showed that asparagine synthetase positive expression in dysplastic surgical margins and its higher expression was correlated with tumor recurrence and local relapse-free survival. INTERPRETATIONS: We developed a panel of metabolic molecular markers to supplement the evaluation of negative and dysplastic margins. FUND: This study was supported by Nanjing Municipal Key Medical Laboratory Constructional Project Funding (Since 2012); Center of Nanjing Clinical Medicine Tumor (Since 2014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Electrochemotherapy in Skin Malignancies of Head and Neck Cancer Patients: Clinical Efficacy and Aesthetic Benefits.

Skin malignancies of the head and neck inflict significant structural, functional, and cosmetic burdens upon those affected. We retrospectively addressed electrochemotherapy anti-tumour efficacy in head and neck skin cancer patients who were not suitable for standard treatments. Scars' physical characteristics and aesthetics were evaluated using validated scar assessment scales. Among 33 treated patients, 82% experienced a complete tumour response while 18% experienced a partial response. At a median time period of 7 months, 96% of the evaluated scars came close to resembling the normal surrounding skin showing excellent results in terms of restoration to original condition with no deformity and/or distortion and in terms of preservation of functionality, such as oral competence and eye protection. Electrochemotherapy is an effective local anticancer procedure for cutaneous tumours. In the treatment of skin malignancies of the head and neck, especially in non-surgical cases, in the elderly and in patients declining surgery, electrochemotherapy may represent a valid alternative to standard management.

Impact of smoking on pathological features in oral cavity squamous cell carcinoma.

OBJECTIVES: We sought to determine whether smokers with oral cavity squamous cell carcinoma (OCSCC) have tumors with more adverse pathological features than in nonsmokers and whether or not these are predictive of outcomes. MATERIALS AND METHODS: We retrospectively identified 163 patients with American Joint Committee on Cancer stages I-IVa OCSCC diagnosed between 2005 and 2015 and treated with curative intent. A pathological risk score (PRS) was calculated using the National Comprehensive Cancer Network adverse risk factors: positive margin, extracapsular extension of lymph node metastases, pT3 or pT4 primary, N2 or N3 nodal disease, perineural invasion, and lymphovascular space invasion. Multivariable models were constructed to determine the independent predictors of overall survival (OS), recurrence-free survival (RFS), and PRS. RESULTS: A total of 108 (66.26%) were smokers and 55 nonsmokers. Three-year actuarial OS and RFS were 62% and 68% in smokers and 81% and 69% in nonsmokers, respectively (P = 0.06 and P = 0.63). Smokers were more likely to have advanced disease stage and tumors with aggressive pathological features than nonsmokers. Smokers had significantly worse PRS (mean ± standard deviation; 2.38 ± 2.19, median; 2.00) than nonsmokers (0.89 ± 1.21, 0.00) (P < 0.001). Older age, higher PRS, and smoking status were independent predictors of OS. Smoking or PRS did not predict for worse RFS. On multivariate analysis, independent predictors of PRS were smoking status and grade (P < 0.001). CONCLUSION: In patients with OCSCC, smokers have more aggressive disease as evidenced by more adverse pathological features than nonsmokers. Moreover, smoking is an independent predictor of OS but not RFS. The PRS is a significant predictor of OS and needs validation in the future studies.

High-dose versus standard-dose radiation therapy for cervical esophageal cancer: Retrospective single-institution study.

BACKGROUND: To evaluate the role of definitive radiotherapy using higher-than-standard-dose radiation of 50 Gy for carcinoma of the cervical esophagus (CCE). METHODS: We reviewed 79 patients with stage I-III CCE, treated between 2000 and 2012. Patients received 5-fluorouracil/cisplatin-based chemotherapy concurrently and were divided into high-dose (≥59.4 Gy, n = 44) and standard-dose (<59.4 Gy, n = 35) groups. RESULTS: The median follow-up was 35 months for surviving patients. The high-dose group had significantly better 3-year local (90.0% vs 60.4%, P = .001) and locoregional (70.4% vs 45.3%, P = .04) control. Progression-free (45.4% vs 37.5%, P = .32) and overall (58.4% vs 49.1%, P = .69) survival rates were not different. High-dose radiation was an independent prognostic factor for locoregional control (P = .04). No differences in late toxicities (esophageal stenosis or tracheoesophageal fistula) were observed. CONCLUSION: High-dose radiation for CCE improves local and locoregional control, without increasing severe toxicities.

Comparison of contemporary staging systems for oropharynx cancer in a surgically treated multi-institutional cohort.

BACKGROUND: Between the publication of the Union of International Cancer Control staging system (UICC) 7th and 8th editions, other staging algorithms for oropharyngeal squamous cell carcinoma (OPSCC) were proposed from Radiation Therapy Oncology Group (RTOG), MD Anderson Cancer Center (MDACC), and Yale University. METHODS: With C-statistics, the above-mentioned five staging algorithms were compared for overall and relapse-free survival endpoints in a multi-institutional cohort of OPSCC cases (n = 338) treated with primary surgery. RESULTS: Pathological UICC 8th ed yielded the highest C-indexes in the entire cohort and in the HPV- subset, whereas MDACC was superior for HPV+ OPSCC. RTOG was the simplest and holistic algorithm with a noninferior discriminatory power. CONCLUSION: UICC 8th ed, MDACC, and RTOG offer moderate and comparable efficacy for staging in this OPSCC patient cohort undergoing surgical treatment. Notable discrepancy between clinical and pathological UICC 8th ed algorithms poses potential concerns in diagnosis, treatment, research, and data management.

A Population-Based Study of Outcomes in Surgically Resected T3N0 Non-Small Cell Lung Cancer in The Netherlands, Defined Using TNM-7 and TNM-8; Justification of Changes and an Argument to Incorporate Histology in the Staging Algorithm.

OBJECTIVE: The objective was to study outcomes in patients in a population registry who were surgically staged as having pT3N0 NSCLC according to the seventh and eighth editions of the TNM staging classification. METHODS: Details of patients who underwent surgery for NSCLC staged as pT3N0M0 from 2010 to 2013 on the basis of the seventh edition of the TNM classification were retrieved from the Netherlands Comprehensive Cancer Organization. These data were next matched with corresponding pathology data from a nationwide registry. Patients were categorized into four major pT3 subgroups as follows: those with a tumor diameter more than 7 cm, those with separate tumor nodules in the same lobe (two or more nodules), those with parietal pleural invasion, and a mixed group (consisting mainly of those with a tumor diameter larger than 7 cm combined with parietal pleural invasion). RESULTS: A total of 683 patients were eligible for analysis. The 3- and 5-year overall survival (OS) rates for the subtype tumor diameter larger than 7 cm were 59.9% and 47.2%, respectively, and were comparable to the rates for the subtype with pleural invasion (50.4% and 45.3%), respectively. The mixed group had worse 3- and 5-year OS rates (37.5% and 28.7%, respectively), which were comparable to the outcomes for TNM eighth edition-staged IIIB and pT4 cases in the International Association for the Study of Lung Cancer database. For the subtype two or more nodules, the 3- and 5-year OS rates were 70.6% and 62.8%, respectively, with patients with adenocarcinoma showing a significantly better OS than did patients with squamous cell carcinoma: a 5-year OS rate of 65.1% versus 47.2%, respectively (p < 0.001), suggesting that the prognosis for the adenocarcinoma subgroup may be comparable to that for the pT2 category, whereas squamous cell carcinoma nodules can remain pT3. CONCLUSION: This population analysis of overall survival rate by pT3N0 subcategory for NSCLC suggests that histologic type is a relevant descriptor in the category two or more nodules. The findings do not support migration of the group with a tumor diameter larger than 7 cm to the category pT4in the eighth edition of the TNM classification, and they suggest that a combination of two pT3 descriptors (the mixed group) merits migration to pT4.

Combined Treatment with Autologous CIK Cells, Radiotherapy and Chemotherapy in Advanced Cervical Cancer.

To investigate the clinical efficacy of autologous cytokine induced killer (CIK) cells transfusion combined with radiochemotherapy in the treatment of advanced cervical cancer. A total of 89 hospitalized patients with advanced cervical cancer were admitted and divided into the treatment group (44 cases, autologous CIK cells transfusion combined with radiochemotherapy) and the control group (45 cases, radiochemotherapy) by a randomized non-blind method. Comparisons of therapeutic efficacies, immune functions, life qualities and survival rates were analyzed between the two groups. The short-term therapeutic efficacy of the treatment group was significantly higher than that of the control group. There was no significant difference in 1, 2 and 3 year survival rates between the two groups. Compared with pre-treatment, levels of CD3+, CD4+/CD8+ in peripheral blood were increased in the CIK group, which were reduced in the control group. In the CIK group,only the feeling was depressed on the 25th day post-treatment (T25) compared with the day before treatment (B1). However in the control group, the function of body, role, social and holistic health was obvious disordered on day T25 compared with day B1. On day T25, there were significant differences in function of body, social and holistic health between two groups. Autologous CIK cells transfusion combined with radiochemotherapy shows better short-term efficacy than radiochemotherapy alone in the treatment of advanced cervical cancer, which obviously improves immune function and life quality of patients with low side effects.

Elderly Patients with Advanced Head and Neck Carcinoma: Does Aggressive Treatment Result in Better Outcomes?

OBJECTIVE: There are no well-defined treatment recommendations for elderly patients with advanced head and neck squamous cell carcinoma. This study aimed to investigate whether aggressive treatment among the elderly translated into better survival outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary institution. SUBJECTS AND METHODS: Elderly patients (≥60 years) with advanced-stage head and neck squamous cell carcinoma (stage III and IV) treated between January 1991 and May 2014 were reviewed. According to current National Comprehensive Cancer Network guidelines, they were classified to have received standard or substandard treatment. Overall survival (OS), locoregional recurrence-free survival, and distant recurrence-free survival were evaluated. RESULTS: A total of 355 patients were treated curatively: 194 with up-front surgery and 161 with radiotherapy or concurrent chemotherapy and radiotherapy. Median OS was higher among patients who received standard treatment (42.0 vs 16.0 months, P < .001). On multivariate analysis, standard treatment showed superior OS ( P < .001). Use of substandard treatment showed a hazard ratio of 2.09 (95% CI, 1.59-2.74) for poorer OS. CONCLUSION: Aggressive standard treatment protocols should be advocated for elderly patients, where comorbidities permit, as they confer better outcomes.

Requiem for Nigro or is anal squamous carcinoma still a surgical problem: Abdominoperineal excision rather than a defunctioning stoma?

BACKGROUND: Combined multimodal treatment (CMT) is the preferred treatment for anal squamous carcinoma with radical surgery reserved for treatment failure. Some patients require a defunctioning stoma prior to CMT. Successful closure of such a stoma is unlikely. Abdominoperineal excision (APE) may be suitable as primary treatment in these patients. METHOD: A retrospective review of all patients with anal squamous carcinoma was undertaken. Patients who required defunctioning colostomies prior to CMT were analysed for potential resectability of tumour prior to CMT and rate of permanent stoma. OBJECTIVE: To evaluate organ preservation in the treatment of anal squamous cancer and the closure rate of pre-treatment, temporary diverting colostomy, thereby assessing whether APE could be offered as primary treatment in those requiring a pre-treatment colostomy. RESULTS: One hundred and twenty-five patients were included of which 58 were males. The mean age was 56 years. 107 were treated with curative intent. Six received primary APE and 12 salvage APE. Thirty (22 males) required pretreatment diverting colostomies. Three (10%) stomas were successfully reversed. Forty-eight (38%) of the 125 completed treatment with a permanent colostomy. Six patients who needed a stoma prior to CMT were deemed resectable. CONCLUSION: Organ preservation was not possible in about a third of patients. Defunctioning stomas prior to CMT were likely to be permanent. We propose that APE could be considered as an alternative in selective cases where the tumour is resectable with low morbidity and a stoma is indicated.

Real world survival data of a rare malignancy: Anal cancer results in HIV negative patients from Turkey.

BACKGROUND/AIMS: An organ preservation approach using chemoradiotherapy has been established for anal cancer. This retrospective cohort study aimed to define the clinico-demographic characteristics and outcomes of cases of human immunodeficiency virus (HIV)-negative anal carcinoma during a period of 20 years in a single comprehensive cancer institute. MATERIALS AND METHODS: This was a single-center retrospective cohort study of patients who were treated between January 1995 and January 2015. The primary outcome measures that were investigated included overall survival (OS), progression-free survival (PFS), colostomy rates, and colostomy-free survival (CFS). RESULTS: A total of 28 patients who were principally treated with standard 5-fluorouracil + mitomycin combination chemoradiotherapy were eligible for analysis. The 3- and 5-year PFS rates were 92.4% and 63%, respectively. The lower T stage was found to be associated with a prolonged PFS (p=0.001). The 3- and 5-year CFS rates were 84.3% and 74.9%, respectively. A longer CFS was observed with lower T stages (p=0.05). At the last follow-up, 75% of the patients with anal cancer were alive, and 71.4% of the patients were disease free. The median OS was not reached with a median follow-up of 54 months (range, 6-115 months). The 3- and 5-year OS rates were 82% and 71.1%, respectively. No late toxicity was observed during the follow-up period. DISCUSSION: The short- and long-term prognoses of HIV-negative patients with anal squamous cell carcinoma were good, and low-grade toxicity was rare, thereby demonstrating that these patients can be successfully treated in a real-life setting with favorable outcomes.

Association of Survival With Shorter Time to Radiation Therapy After Surgery for US Patients With Head and Neck Cancer.

IMPORTANCE: Shortening the time from surgery to the start of radiation (TS-RT) is a consideration for physicians and patients. Although the National Comprehensive Cancer Network recommends radiation to start within 6 weeks, a survival benefit with this metric remains controversial. OBJECTIVE: To determine the association of delayed TS-RT with overall survival (OS) using a large cancer registry. DESIGN, SETTING, AND PARTICIPANTS: In this observational cohort study, 25 216 patients with nonmetastatic stages III to IV head and neck cancer were identified from the National Cancer Database (NCDB). EXPOSURES: Patients received definitive surgery followed by adjuvant radiation therapy, with an interval duration defined as TS-RT. MAIN OUTCOMES AND MEASURES: Overall survival as a function of TS-RT and the effect of clinicopathologic risk factors and accelerated fractionation. RESULTS: We identified 25 216 patients with nonmetastatic squamous cell carcinoma of the head and neck. There were 18 968 (75%) men and 6248 (25%) women and the mean (SD) age of the cohort was 59 (10.9) years. Of the 25 216 patients, 9765 (39%) had a 42-days or less TS-RT and 4735 (19%) had a 43- to 49-day TS-RT. Median OS was 10.5 years (95% CI, 10.0-11.1 years) for patients with a 42-days or less TS-RT, 8.2 years (95% CI, 7.4-8.6 years; absolute difference, -2.4 years, 95% CI, -1.5 to -3.2 years) for patients with a 43- to 49-day TS-RT, and 6.5 years (95% CI, 6.1-6.8 years; absolute difference, -4.1 years, 95% CI, -3.4 to -4.7 years) for those with a 50-days or more TS-RT. Multivariable analysis found that compared with a 42-days or less TS-RT, there was not a significant increase in mortality with a 43- to 49-day TS-RT (HR, 0.98; 95% CI, 0.93-1.04), although there was for a TS-RT of 50 days or more (HR, 1.07; 95% CI, 1.02-1.12). A significant interaction was identified between TS-RT and disease site. Subgroup effect modeling found that a delayed TS-RT of 7 days resulted in significantly worse OS for patients with tonsil tumors (HR, 1.22; 95% CI, 1.05-1.43) though not other tumor subtypes. Accelerated fractionation of 5.2 fractions or more per week was associated with improved survival (HR, 0.93; 95% CI, 0.87-0.99) compared with standard fractionation. CONCLUSIONS AND RELEVANCE: Delayed TS-RT of 50 days or more was associated with worse overall survival. The multidisciplinary care team should focus on shortening TS-RT to improve survival. Unavoidable delays may be an indication for accelerated fractionation or other dose intensification strategies.

The Impact of Skeletal Muscle Depletion on Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Skeletal muscle depletion and sarcopenia have been reported as poor prognostic factors for several types of cancer. The aim of this study was to investigate the prognostic impact of skeletal muscle depletion and sarcopenia on the outcomes in head and neck cancer patients. METHODS: Patients with head and neck squamous cell carcinoma (HNSCC) treated from January 2013 to June 2014 were included in this study. The pretreatment cross-sectional area of skeletal muscle at the third lumbar vertebra (L3) was measured by computed tomography image analysis using the ImageJ software. L3 skeletal muscle index (SMI) and fat-free mass (FFM) were calculated. RESULTS: Eighty-five patients with HNSCC were included. The cut-off value of sarcopenia was set at SMI <46.7 cm2/m2 (males) and 30.3 cm2/m2 (females). The cut-off value of FFM was set at 42.3 kg (males) and 30.6 kg (females). Patients with a low SMI (sarcopenia) and low FFM had a significantly poorer prognosis than others, especially those who received definitive radiotherapy. Sarcopenia and low FFM are independent factors for poor prognosis in patients with HNSCC. CONCLUSION: The skeletal muscle area at L3 should be calculated when considering treatment options for head and neck cancer.

Free Flap Transfer for Head and Neck Reconstruction Using Local Anesthesia in Elderly Patients.

BACKGROUND: The incidence of skin cancer appearing on the head and neck areas is higher in elderly patients. Although free flap reconstruction is the mainstay after tumor excision, it is challenging to complete in elderly patients, owing to the high risk of complications and/or mortality rates associated with the use of general anesthesia. In this study, we used only local anesthesia in free tissue reconstruction of the head and neck in five elderly patients. MATERIALS AND METHODS: From 2013 to 2016, 5 elderly patients with high risk of general anesthesia underwent reconstruction with either anterolateral thigh free flaps or groin free flap under local anesthesia, after wide excision of malignant tumors at head and neck. For each patient, the following information was collected: age, gender, body weight, anesthesia agents, intravenous fluid, blood loss, site of lesion, flap size, operation time, complications, and follow-up time. RESULTS: All flaps survived completely. The mean age of 5 patients (3 male patients and 2 female patients) was 84 years (range, 68-100 years), and mean flap size was 199.6 cm (range, 120-330 cm). The mean follow-up period was 26.6 months (range, 5-38 months). No complications were found. CONCLUSIONS: With proper local anesthesia, successful head and neck reconstruction with free flap was possible, and patient prognosis was positive. There are numerous advantages, including: (1) a safer and inexpensive operation; (2) no complications from general anesthesia; (3) the fact that free flap transfer can be performed in elderly patients, even if they cannot tolerate general anesthesia; and (4) allowance of the performance of free tissue transferring in countries without adequate medical resources.

Malignancy Risk and Recurrence with Psoriasis and its Treatments: A Concise Update.

Psoriasis is a common inflammatory cutaneous disease that affects approximately 120 million people worldwide. Systemic treatments have significantly improved disease burden, but concerns persist regarding their association with increased risk of malignancy. Patients with psoriasis have a slightly elevated baseline risk of lymphoproliferative diseases. Studies on methotrexate and cyclosporine, as well as older biological agents such as tumor necrosis factor inhibitors, have found no increased risk of non-cutaneous solid tumors; however, positive associations between cutaneous squamous cell carcinomas and certain therapies have been found. There is conflicting evidence regarding the risk of lymphoma and melanoma. Further studies are needed to determine the long-term safety of newer psoriasis treatments (interleukin [IL]-12/23, IL-17, Janus kinase 1/3, and phosphodiesterase-4 inhibitors), specifically their safety in patients with a history of cancer. This review summarizes the most recent studies on malignancy risk from psoriasis, and its treatments in patients and cancer survivors, with the highest available level of evidence.