Primary Chemoradiation Research Articles

Impact of social services on depression and treatment outcomes amongst women with locally advanced cervix cancer

Objective: The purpose of this study was to examine the impact of interventions targeted at depression and sociodemographic barriers to care on outcomes of patients with locally advanced cervical cancer (LACC) undergoing primary chemoradiation.

Response evaluation of cervical lymph nodes after chemoradiation in patients with head and neck cancer - does additional [18F]FDG-PET-CT help?

BackgroundContrast-enhanced high-resolution computed tomography (contrast-CT) is a standard imaging modality following primary concurrent radiochemotherapy (RCT) for response evaluation in patients with head and neck squamous cell carcinoma (HNSCC). We investigated the additional benefit of Fluorine-18-fluorodeoxyglucose ([18F]FDG) - positron emission tomography with computed tomography (PET-CT), if complete response (CR) in the neck based on contrast-CT was considered unsafe by the interdisciplinary tumor board (ITB).MethodsIn a retrospective observational study, patients recorded in the institutional tumor registry with incident advanced HNSCC following first line treatment with RCT were eligible. If contrast-CT results of the neck were equivocal or positive at response evaluation, a neck dissection (ND) was scheduled. While waiting for the ND, a [18F]FDG-PET-CT was performed in addition. The histopathological outcome of ND served as reference criterion. Accuracy parameters including sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for both, contrast-CT and PET-CT, served as main outcome parameters.ResultsA total of 41 HNSCC patients with positive or equivocal posttreatment contrast-CT were eligible for post-RCT-ND. Of these, 33 received an additional [18F]FDG-PET-CT prior to surgery. Median interval between completion of RCT and the ([18F]FDG)-PET-CT was 10 weeks. Vital persistent tumor in the neck was histopathologically found in 13 of 33 patients with positive or equivocal posttreatment contrast-CT. For contrast-CT and [18F]FDG-PET-CT, sensitivity was 92.3 and 69.2% and did not differ statistically significantly (p = 0.250) whereas specificity was significantly higher for [18F]FDG-PET-CT compared with contrast-CT (80% vs. 25%, p = 0.001). For contrast-CT and [18F]FDG-PET-CT accuracy, PPV and NPV was 31.7, 12.0,96.7 and 78.9, 27.8,95.0%, respectively.ConclusionA negative [18F]FDG-PET-CT did not improve the exclusion of persistent vital tumor in the neck after primary RCT in comparison with contrast-CT alone. However, a positive [18F]FDG-PET-CT was a considerably better indicator of persistent, vital tumor in the neck than contrast-CT. If, based on the [18F]FDG-PET-CT result, the ND in patients with an uncertain or positive neck response in contrast CT had been omitted, the treatment of persistent nodal disease would have been delayed in 3 of 13 patients. On the other hand, if ND would have only been performed in [18F]FDG-PET-CT positive patients, an unnecessary ND would have been avoided in 11 of 20 patients.

2D and 3D convolutional neural networks for outcome modelling of locally advanced head and neck squamous cell carcinoma

For treatment individualisation of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with primary radiochemotherapy, we explored the capabilities of different deep learning approaches for predicting loco-regional tumour control (LRC) from treatment-planning computed tomography images. Based on multicentre cohorts for exploration (206 patients) and independent validation (85 patients), multiple deep learning strategies including training of 3D- and 2D-convolutional neural networks (CNN) from scratch, transfer learning and extraction of deep autoencoder features were assessed and compared to a clinical model. Analyses were based on Cox proportional hazards regression and model performances were assessed by the concordance index (C-index) and the model’s ability to stratify patients based on predicted hazards of LRC. Among all models, an ensemble of 3D-CNNs achieved the best performance (C-index 0.31) with a significant association to LRC on the independent validation cohort. It performed better than the clinical model including the tumour volume (C-index 0.39). Significant differences in LRC were observed between patient groups at low or high risk of tumour recurrence as predicted by the model (p=0.001). This 3D-CNN ensemble will be further evaluated in a currently ongoing prospective validation study once follow-up is complete.

Long-term results of robotic radiosurgery for non brachytherapy patients with cervical cancer

BackgroundConsolidation brachytherapy is a critical treatment component for cervical cancer patients undergoing primary chemoradiation. Some patients are unsuitable for brachytherapy for a variety of reasons. The use of alternatives (LINAC-based stereotactic radiosurgery or external beam boosts) compromise oncologic results in cervical cancer patients. Thus, we evaluated the value of brachytherapy-like doses prescriptions using robotic radiosurgery (CyberKnife®, CR, Acuuray, Sunnyvale, CA, USA).MethodsFrom 06/2011 to 06/2015, 31 patients (median age 53 years; range 30–77 years) with histologically proven FIGO stages IB-IVB cervical cancer underwent primary chemoradiation. All patients were either not suitable for intracervical brachytherapy for a variety of reasons or refused the brachytherapy. To achieve an adequate dose within the tumor, a CK boost was applied after fiducial implantation. In 29 patients, a dose of either five times 6 Gy or five times 5 Gy was prescribed to the target volume. Two patients received three times 5 Gy. The target dose was prescribed to the 70% isodose. Treatment toxicity was documented once weekly regarding vaginal mucositis, bladder, and bowel irritation according to CTCAE v. 4.03. If possible 3 months after completion of treatment intracervical curettage was performed to exclude residual tumor and the patients were followed up clinically. Sparing of organs at risk (OAR) and outcome in terms of local control (LC), overall survival (OS), and progression-free survival (PFS) were assessed.ResultsOf the 31 patients, 30 have completed CK boost therapy. The median follow-up time was 40 months (range 5–84 months). General treatment tolerability was good. Except for 1 patient, who had diarrhea grade 3, no treatment related side effects above grade 2 were reported. Sparing of OAR was excellent. The 1‑, 3‑, and 5‑year OS rates were 89, 60, and 57% respectively across all stages. Seven patients showed progression (28%), only two of them with local relapse (8%), resulting in an LC rate of 92% after 3 and 5 years. Mean PFS was 41 months (range 2–84 months). Patients with local recurrence had PFS of 5 and 8 months. Five patients developed distant metastases. Fifteen patients (48%) underwent intracervical curettage 3 months after completion of treatment of which 14 (93%) had complete pathologic response.ConclusionBrachytherapy remains the standard of care for patients diagnosed with cervical cancer and indication for primary chemoradiation. In terms of local control, CyberKnife®-based boost concepts provide excellent local control. It can be an alternative for patients who cannot receive adequate brachytherapy. Distant relapse still remains a challenge in this context.

Implications of Treatment Modality on Chronic Opioid Use Following Treatment for Head and Neck Cancer.

To investigate the relationship between treatment modality and chronic opioid use in a large cohort of patients with head and neck cancer. Retrospective cohort study. Single academic center. There were 388 patients with head and neck cancer treated between January 2011 and December 2017 who met inclusion criteria. Clinical risk factors for opioid use at 3 and 6 months were determined with univariate and multivariate analyses. The prevalence of opioid use was 43.0% at 3 months and 33.2% at 6 months. On multivariate analysis, primary chemoradiation (odds ratio [OR], 4.04; 95% CI, 1.91-8.55) and surgery with adjuvant chemoradiation (OR, 2.39; 95% CI, 1.09-5.26) were associated with opioid use at 3 months. Additional risk factors at that time point included pretreatment opioid use (OR, 7.63; 95% CI, 4.09-14.21) and decreasing age (OR, 1.03; 95% CI, 1.01-1.06). At 6 months, primary chemoradiation (OR, 2.40; 95% CI, 1.34-4.28), pretreatment opioid use (OR, 5.86; 95% CI, 3.30-10.38), current tobacco use (OR, 2.00; 95% CI, 1.18-3.40), and psychiatric disorder (OR, 1.79; 95% CI, 1.02-3.14) were associated with opioid use. Of the patients who receive different treatment modalities, those receiving primary chemoradiation are independently at highest risk for chronic opioid use. Other risk factors include pretreatment opioid use, tobacco use, and a psychiatric disorder. In an effort to reduce their risk of chronic opioid use, preventative strategies should be especially directed to these patients.

Socially determined cervical cancer care navigation: An effective step toward health care equity and care optimization.

Despite being the standard of care for patients with locoregional cervical cancer, many patients do not complete all components of primary chemoradiotherapy (pCRT): external beam radiotherapy, chemosensitization, and brachytherapy. Incomplete or protracted pCRT is associated with worse survival. The authors implemented a socially determined cervical cancer care navigation program at a public safety-net hospital to improve treatment adherence. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB1 to IVA cervical cancer who underwent pCRT from 2012 to 2016 were prospectively enrolled into this navigation program spanning the medical, financial, and psychosocial aspects of care. This patient cohort was compared with a similar cohort of consecutive nonnavigated patients who were treated from 1998 to 2008. Patient characteristics, treatment data, and patient outcomes were collected. A database of navigation encounters was maintained prospectively. A total of 46 patients composed the navigated cohort and 85 patients composed the nonnavigated cohort. After implementation of the cervical cancer care navigation program, the percentage of patients receiving ≥5 cycles of weekly cisplatin increased from 74% to 93% (P<.01) and rates of the initiation of brachytherapy during external beam radiotherapy increased from 49% to 78% (P<.01). The median treatment time was reduced from 67 days in the nonnavigated patients to 55 days in the navigated patients (P<.01). Approximately 95% of navigated patients who completed pCRT did so within 63 days, compared with 52% of nonnavigated patients (P<.01). Treatment completion within 63 days was associated with significantly improved overall survival. Socially informed cervical cancer care navigation can significantly improve the timeliness of guideline-based care, enhance access to resources for underserved minority patients receiving pCRT, and may improve overall patient outcomes.

The effect of guideline-concordant care in mitigating insurance status disparities in cervical cancer

ObjectiveTo evaluate whether the receipt of evidence-based care could mitigate survival disparities among Medicaid recipients and uninsured women with cervical cancer. MethodsThe National Cancer Database was utilized to identify women with cervical cancer treated from 2004 to 2016. Eight quality metrics were determined. Survival outcomes were examined stratified by insurance status and stage. To measure the impact of guideline-concordant care on the mitigation of disparities, we compared survival outcomes of the overall cohort to one that was perfectly adherent to all quality metrics. ResultsA total of 103,400 patients were identified; 47.0% of patients had private insurance, 21.5% Medicaid and 9.2% uninsured. Medicaid and uninsured patients were significantly less likely than privately insured patients to receive timely completion of radiation and timely initiation of treatment; uninsured patients were also significantly less likely to receive treatment for locally advanced disease. Medicaid and uninsured patients were also less likely to receive lymph node assessment and primary chemoradiation. Medicaid and uninsured patients had an increased risk of mortality compared to privately insured patients (aHR = 1.36, 95% CI 1.31–1.41 and aHR 1.29, 95% CI 1.23–1.36 respectively). While the receipt of these quality metrics was associated with improved survival, Medicaid and uninsured women who received guideline-concordant care were still at an increased risk of death compared to women with private insurance (aHR = 1.38, 95% CI 1.35–1.49 and aHR = 1.24; 95% CI, 1.16–1.32 respectively). ConclusionMedicaid and uninsured patients were less likely to receive evidence-based care and were at increased risk of mortality at all stages compared to privately insured patients. The receipt of quality care does not eliminate insurance status-based disparities among women with cervical cancer.

Insurance Status as a Predictor of Treatment in Human Papillomavirus Positive Oropharyngeal Cancer.

The link between human papillomavirus (HPV) and oropharyngeal cancer (OPC) is well known. Locally advanced, HPV-positive OPC (HPV OPC) can be treated with either chemoradiation or primary surgery with or without adjuvant therapy. Head and neck cancer patients with government insurance or uninsured have been shown to have worse prognosis than similar patients with private insurance. In this study, we aimed to determine if insurance status would predict treatment modality in patients with HPV OPC. A retrospective analysis using the National Cancer Database (NCDB). The National Cancer Database was used to identify patients with HPV OPC who underwent primary surgery or primary chemoradiation from 2010-2015. Insurance status was categorized as government, private, or no insurance. The relationship between insurance status and treatment was investigated using Chi square and multivariate regression models. Kaplan-Meier analyses were performed comparing overall survival (OS) by insurance status. There were 10,606 patients were included. There was a statistically significant correlation between insurance status and primary treatment modality for HPV OPC (P < .001). Patients with government insurance were 19.3% less likely to undergo surgery and uninsured patients were 36.9% less likely to undergo primary surgery when compared to those with private insurance (P < .001), even after correcting for TNM stage in multivariate analysis. There was an improved 5-year OS for patients with private insurance (86.6%) versus both government insurance (68.4%) and no insurance (69.9%) (P < .001). Patients with private insurance are more likely to undergo primary surgery in HPV OPC and have improved overall survival. 4 Laryngoscope, 131:776-781, 2021.

Salvage Resection for Isolated Local and/or Regional Failure of Head/Neck Cancer Following Definitive Concurrent Chemoradiotherapy Case Series and Review of the Literature

Primary management of advanced head/neck cancers involves concurrent chemoradiotherapy . Subsequently, regional and local failures are managed with resection but there have been few reports that describe the morbidity and disease control outcomes of surgical salvage in this setting. Retrospective analysis describes complications, survival, and patterns of failure after salvage resection of isolated local and/or regional failures of head/neck cancer following definitive concurrent chemoradiotherapy. Sixteen patients were identified for inclusion: laryngectomy in 11 patients, oral cavity/oropharynx resection in 2 patients, and neck dissection alone in 4 patients. Ten patients required graft tissue reconstruction (6 pedicle and 4 free flap). Median post-operative hospitalization was 7 days (range 3-19), and 4 patients required hospital re-admission. At a median survivor follow-up of 15.8 months (range 4.3-34.9), 10 patients were alive (6 without evidence of disease). Seven patients experienced disease recurrence at a median 6.7 months (range 0-12.6) following salvage resection (2 with isolated distant failures). Estimated 2-year local/regional control, freedom from failure, and overall survival were 58%, 39%, and 58%, respectively. Surgical salvage after primary definitive concurrent chemoradiotherapy is feasible with toxicity and outcomes similar to prior radiotherapy alone or sequential chemotherapy and radiation. Local andregional recurrence remains the predominant pattern of failure.

Preventive use of gabapentin to decrease pain and systemic symptoms in patients with head and neck cancer undergoing chemoradiation

Radiation for patients with head and neck cancer (HNC) is associated with painful mucositis that impacts the delivery of treatment and contributes to high symptom burden. This was a prospective, randomized pilot trial. Eligible patients received primary or adjuvant chemoradiation. Patients were randomized to usual care vs usual care plus gabapentin titrated to drug tolerance during radiation. Patients completed a symptom survey at baseline and weekly during therapy. Seventy-nine patients were enrolled in the study (38 control, 41 treatment). At interim analysis, gabapentin use resulted in a decrease in pain (P = .004), with the biggest decreases being in the latter weeks of therapy. By week 7, the median pain score in the treatment group was below the 0.25 quantile of the control group. Prophylactic use of gabapentin during chemoradiation for HNC patients resulted in a decrease in pain, neurosensory symptoms, and general systemic symptoms.

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

BackgroundFor 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.MethodsTopROC 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.DiscussionThis 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 registrationNCT03691441 Registered 1 October 2018 - Retrospectively registered.

PET-detected asymptomatic recurrence is associated with improved survival in recurrent cervical cancer.

We aimed to examine utilization patterns of positron emission tomography scans (PET or PET/CT) beyond 6months after cervical cancer treatment. We investigated survival outcomes of asymptomatic patients with PET-detected recurrence. We performed a retrospective review of 283 patients with stage IA-IVA cervical cancer treated with primary chemoradiation. The 107 patients (37.8%) with recurrence were categorized as "asymptomatic PET-detected recurrence" (n = 23) or "standard detection" (n = 84) and wecompared clinical characteristics and outcomes using multivariate logistic regression analysis. Late post-treatment PET (≥ 6months after treatment) was performed in 35.3% (n = 100). Indications for late post-treatment PET included restaging in setting of known recurrence (23.6%), follow up of prior ambiguous imaging findings (9.7%), and new symptoms or exam findings (6.7%). However, late post-treatment PET was most commonly performed outside of current imaging guidelines, in asymptomatic patients without suspicion for recurrence (60.0%), presumably for surveillance. The median time to recurrence was 12.1months (IQR 7.3-26.6). 23 patients (21.5%) had recurrence detected late post-treatment PET while asymptomatic (n = 23/107). Patients with asymptomatic PET-detected recurrence had improved survival by 26.3months compared to the standard detection cohort (50.3 vs 24.0months, p = 0.0015). On multivariate analysis, predictors of survival after recurrence were presence of distant metastases at diagnosis (p = 0.010) and asymptomatic PET-detected recurrence (p = 0.039). PET imaging in asymptomatic patients beyond 6months after treatment may have clinical benefit and warrants further study. Detection of recurrence by PET inasymptomatic patients ≥ 6months after chemoradiation was associated with prolonged survival by more than 2years.

Discussion of Prophylactic Use of the Pectoralis Major Flap to Prevent Anastomotic Leak in the Reconstruction of a Total Laryngopharyngoesophagectomy Defect Combined With Gastric Pull-Up After Chemoradiotherapy.

Total laryngopharyngoesophagectomy defects after surgical ablation for laryngopharyngeal carcinoma with involvement of the cervical esophagus represents a challenge to the reconstructive surgeon. Complicating an already challenging operation is when surgical ablation occurs after failure of primary chemoradiation requiring the surgeon to operate and reconstruct in an irradiated field limiting potential reconstructive options. Due to the advanced stage at diagnosis, some studies have shown that while traditional management with radiotherapy may be considered as an initial treatment modality, often times this has failed to provide sustainable improvement in survival with reported high local recurrence rates. With relatively high local recurrence rates following radiotherapy, movement towards aggressive surgical resection is favored in some institutions. Despite this movement, primary treatment with chemoradiation is still commonly used as a primary modality opening up the opportunity for residual or recurrent disease leading the surgeon to perform salvage surgery to eradicate disease after primary treatment failure. With advanced ablative surgery comes the challenge to find an ideal reconstructive option that will optimize functional outcomes which has shown to be particularly challenging when operating in a post-radiated field with a higher risk for pharyngocutaneous fistulas. The authors present a case where reconstruction of such a defect after local failure with primary chemoradiation was successful using a single stage reconstruction with the gastric pull up technique in combination with a pectoralis major myocutaneous flap. As the risk of anastomotic leak is significantly higher in patients following radiation, this method showed utilizing a prophylactic muscle flap at the time of reconstruction may further bolster the repair and prevent anastomotic leak.

Role of cancer stem cell markers ALDH1, BCL11B, BMI-1, and CD44 in the prognosis of advanced HNSCC

PurposeCancer stem cells (CSCs) are held accountable for the progress of head and neck squamous cell carcinoma (HNSCC). In the presented study, the authors evaluated the prognostic value of CSC markers in two particular HNSCC cohorts.MethodsThis two cohort study consisted of 85 patients with advanced stage HNSCC, treated with primary radio(chemo)therapy (pRCT), and 95 patients with HNSCC, treated with surgery and partially adjuvant radio(chemo)therapy. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were assessed. Samples were assessed for the expression of different molecular stem cell markers (ALDH1, BCL11B, BMI‑1, and CD44).ResultsIn the pRCT cohort, none of the baseline patient and tumor features exhibited a statistically significant relation with survival in either the cohort or the human papillomavirus (HPV)-stratified subcohorts. High expression of BMI‑1 significantly decreased OS and DFS, while high expression of CD44 decreased all modes of survival. Multivariate analysis showed significant prognostic influence for all tested CSC markers, with high BMI‑1 and CD44 decreasing survival (BMI-1: OS, DFS, DSS; CD44: OS, DFS) and high ALDH1 and BCL11B showing a beneficial effect on survival (ALDH1: OS, DFS; BCL11B: OS, DSS). In the surgical cohort, classical prognosticators such as HPV status, R1 resection, and nodal status in HPV-negative HNSCC played a significant role, but the tested CSC markers showed no significant effect on prognosis.ConclusionAlthough validation in independent cohorts is still needed, testing for CSC markers in patients with advanced or late stage HNSCC might be beneficial, especially if many comorbidities exist or disease is irresectable. The findings might guide the development and earlier use of targeted therapies in the future.

Nonsurgical management of resectable oral cavity cancer in the wake of COVID-19: A rapid review and meta-analysis.

Surgery is the preferred treatment modality for oral squamous cell carcinoma (OSCC). However, due to limited resources, re-assessment of treatment paradigms in the wake of the Coronavirus Disease 2019 (COVID-19) pandemic is urgently required. In this rapid review, we described contemporary oncological outcomes for OSCC using non-surgical modalities. A systematic literature search was conducted for articles published between January 1, 2010 and April 1, 2020 on MEDLINE and Cochrane CENTRAL. Studies were included if they contained patients with OSCC treated with either neoadjuvant, induction, or definitive radiotherapy, chemotherapy, immunotherapy, or combination thereof, and an outcome of overall survival. In total, 36 articles were included. Definitive radiotherapy or chemoradiotherapy were the focus of 18 articles and neoadjuvant chemotherapy or chemoradiotherapy were the focus of the other 18 articles. In early stage OSCC, definitive radiotherapy, with or without concurrent chemotherapy, was associated with a significantly increased hazard of death compared to definitive surgery (HR: 2.39, 95% CI: 1.56-3.67, I2: 63%). The hazard of death was non-significantly increased with definitive chemoradiotherapy in studies excluding early disease (HR: 1.98, 95% CI: 0.85-4.64, I2: 84%). Two recent randomized control trials have been conducted, demonstrating no survival advantage to neoadjuvant chemotherapy. This review suggests that primary radiotherapy and chemoradiotherapy are inferior to surgical management for OSCC. Strategies for surgical delay warranting consideration are sparse, but may include several neoadjuvant regimens, recognizing these regimens may not offer a survival benefit over definitive surgery alone.

Management of anal intraepithelial neoplasia and anal squamous cell carcinoma at a tertiary referral centre with a dedicated infectious diseases unit: an 18-year review.

Anal squamous cell carcinoma (ASCC) is a rare malignancy with rising incidence rates. Risk factors include human immunodeficiency virus (HIV) infection, high-risk sexual activity and HPV-related genitourinary dysplasia/neoplasia. There is an overlap between high-risk patients and those attending HIV Medicine/Sexual Health (HMSH) services. We hypothesised that HMSH involvement may facilitate earlier referral to colorectal surgeons, with better outcomes. Retrospective review of all ASCC and anal intraepithelial neoplasia (AIN) treated at a tertiary-referral hospital with a dedicated HMSH clinic between 2000 and 2018. Comparative analysis was performed of demographics, management and outcomes between HMSH and non-HMSH patients. One hundred and nine patients had anal pathology, eighty-five with ASCC (78%) and twenty-four with AIN (22%). Seventy (64%) were male. Median (range) age at ASCC diagnosis was 51 years (26-88). Thirty-six percent of all patients attended HMSH services, 28% were HIV positive, and 41% of males were men-who-have-sex-with-men (MSM). Eighty-one ASCC patients (97.5%) were treated with curative intent. Sixty-seven (80%) had primary chemoradiation therapy. Fifteen (17.5%) had primary surgical excision. Twelve (14%) developed recurrent disease. Ultimately, seven required salvage APR. Overall 3-year survival (3YS) was 76%. HMSH patients were significantly younger at ASCC diagnosis (p < 0.001), with a higher prevalence of HIV, HPV and MSM. HMSH attenders also tended to be diagnosed at earlier stages, were less likely to develop recurrence and achieved better overall outcomes, with a superior overall 3YS than non-HMSH patients (92% vs 72%, p = 0.037). ASCC incidence is increasing worldwide. The HMSH cohort has emerged as a distinct subpopulation of younger, high-risk, male patients. Collaboration between HMSH and colorectal surgeons offers an opportunity for risk reduction strategies and earlier intervention.

Organ preservation in advanced laryngeal/hypopharyngeal carcinoma: lessons from the DeLOS-II trial

Patients with locoregionally advanced laryngeal and hypopharyngeal squamous cell carcinomas (LHSCC) comprise two broad groups: those who are candidates for functional larynx preservation (LP) with avoidance of ablative surgery and those who are not. Currently, treatment depends on the patient's needs and wishes, the experience and recommendation of the surgeon, the philosophy of the institution, etc. The milestone VA trial established non-surgical LP in advanced LHSCC in the 1990s using induction chemotherapy (IC) with PF (cisplatin, P,plus 5‑fluorouracil,F) followed by irradiation (IC + RT) as an appropriate alternative treatment to total laryngectomy (TL). Even though the findings of the VA trial were verified by the EORTC 24891 trial, adebate persists regarding the best protocol for balancing survival and laryngectomy-free survival (LFS) with acceptable late toxicity and good functional outcome. In advanced LHSCC without surgical options for larynx preservation, only IC + RT or primary concurrent platin-based chemoradiotherapy (CRT) are accepted treatment options aiming to preserve afunctional larynx. In the US, cisplatin-based CRT is exclusively recommended as the best curative protocol. With regards to long-term survival with functional organ preservation and persistently high failure rates, there is current discussion on the necessity of improving patient selection based on the current literature and the recently published data of the DeLOS-II trial.

CCTG HN.10: A phase II single-arm trial of elective volume adjusted de-escalation radiotherapy (EVADER) in patients with low-risk HPV-related oropharyngeal squamous cell carcinoma (NCT03822897).

TPS6592 Background: Treatment for HPV positive(+) oropharyngeal squamous cell carcinoma (OSCC) is highly effective but associated with significant short and long term treatment related morbidity. We hypothesize that decreasing the regions of elective nodal irradiation (ENI) in the neck will lead to less toxicity and better quality of life/functional outcomes while maintaining high disease control rates in patients with favourable prognosis HPV+ OSCC. Methods: HN.10 is a Canadian Cancer Trials Group phase II trial with a primary objective to evaluate the efficacy of primary definitive radiotherapy (RT) or chemoradiotherapy (CRT) utilizing volume reduced ENI as measured by 2-year event-free survival (EFS) in patients with low-risk HPV+ OPSCC. Secondary objectives include to evaluate overall survival, local control, regional control, locoregional control, out-of-field regional control, distant metastasis free survival, early and late toxicities of treatment, subjective swallowing functions, quality of life, utilization of healthcare resources, work productivity, and prognostic biomarkers. An imaging and biospecimen bank will be compiled as part of trial conduct. Key eligibility criteria include: pathologically proven diagnosis of HPV+ OPSCC; HPV association determined locally by either p16 immunohistochemistry or direct detection of HPV DNA sequences (e.g. by PCR or in situ hybridization) performed on a core needle or surgical biopsy specimen of the primary tumour or involved cervical lymph node; clinical stage T1-3 N0-1 M0 (UICC/AJCC 8th Ed.); fit for radiotherapy +/-chemoradiotherapy. Statistical Design: The primary endpoint is 2-year EFS. Assuming 2-year EFS to be 91% (Ha) for low-risk HPV-related OPSCC with standard treatment, and that the experimental treatment will be considered as ineffective if the 2-year EFS is ≤ 85% (H0), with one-sided alpha of 0.1, a sample size of 100 patients will have 80% power to detect a 6% difference of 2-year EFS. With 3 years of accrual and 2 years of follow-up, the total duration of this study will be 5 years. A total of 304.7 person-years of follow-up is needed for the final analysis. The null hypothesis (H0) will be rejected when the observed survival rate is 88.85% or higher (i.e. if there are 18 or fewer EFS events observed). Conduct to Date: Study activation February 20, 2019. Enrollment as of January 29 2020: 23. Clinical trial information: NCT03822897 .

Prospective study of biomarkers in squamous cell carcinoma of the anal canal (SCCAC) and their influence on treatment outcomes: Five-year long-term results.

4053 Background: Chemoradiation (CRT) is a curative treatment for SCCAC. However, some patients (pts) present primary CRT resistance. As a rare tumor, there is a lack of prospective studies of prognostic factors in this setting. Methods: This prospective cohort study was aimed to evaluate predictive biomarkers (Ki-67, PD-L1, Human papillomavirus (HPV), HIV status, and tumor DNA mutations) in SCCAC. We published the 6 months (m) response rate (RR) of this cohort showing that HIV- were 5.7 times more likely to achieve response 6m post CRT (OR 5.72, CI 95% 2.5-13.0, P &lt; 0.001). Now we report the long-term follow-up results of 5-year progression-free survival (PFS) and overall survival (OS). Eligible pts had T2-4/N0-3/M0 disease and were candidates to standard CRT. DNA mutations were analyzed by next-generation sequencing (NGS). HPV positivity was tested by PapilloCheck Test. KI-67 and PD-L1 were evaluated by immunohistochemistry. Results: 78 pts were recruited from Jan/2011 to Dec/2015. 75 were evaluable for PFS and OS. The median age was 57 years; 49 (65%) were stage III, and 9 (12%) were HIV+. HPV was evaluated in 67 and found in 47 (70.1%); HPV16 was the most common. PD-L1 was tested in 61; 10 (16.4%) had positive expression &gt; 1%. Ki-67 was performed in 65, with a median of 50% (range 1-90%). The median follow up is 66m. 5-year PFS and OS rates were 63.3% (95% CI 51.2-73.2%) and 76.4% (95% CI 64.8-84.6%), respectively. In a multivariate analysis, age (HR 1.06, P = 0.022, IC 95% 1.01-1.11) and absence of complete response at 6m (HR 3.36, P = 0.007, IC 95% 1.39-8.09) was associated with inferior OS. The OS rate was 62.5% in HIV+ group (95% CI 22.9-86%) in comparison with 78% (95% CI 65.7-86.3%) among HIV- pts, although this difference was not statistically significant (P = 0.400). A tendency to inferior OS was observed among pts with p53 codon 72 polymorphism (HR 2.83, P = 0.181, 95% CI 0.61-13.02). Other tumor mutations, HPV, Ki-67 expression, and PD-L1 expression, were not associated with PFS and OS. Conclusions: HIV- pts were 5.7 times more likely to achieve response 6m post CRT. The absence of complete response at 6m was the main factor associated with poor 5-year OS. New strategies of follow up and complementary treatment should be studied in late responders and HIV+ pts to ensure the success of curative treatment. Clinical trial information: 36211 .

Prophylactic Use of the Pectoralis Major Flap to Prevent Anastomotic Leak in the Reconstruction of a Total Laryngopharyngoesophagectomy Defect Combined With Gastric Pull-Up After Chemoradiotherapy

Total laryngopharyngoesophagectomy defects after surgical ablation for laryngopharyngeal carcinoma with involvement of the cervical esophagus represents a challenge to the reconstructive surgeon. Complicating an already challenging operation is when surgical ablation occurs after failure of primary chemoradiation requiring the surgeon to operate and reconstruct in an irradiated field limiting potential reconstructive options. Due to the advanced stage at diagnosis, some studies have shown that while traditional management with radiotherapy may be considered as an initial treatment modality, often times this has failed to provide sustainable improvement in survival with reported high local recurrence rates. With relatively high local recurrence rates following radiotherapy, movement towards aggressive surgical resection is favored in some institutions. Despite this movement, primary treatment with chemoradiation is still commonly used as a primary modality opening up the opportunity for residual or recurrent disease leading the surgeon to perform salvage surgery to eradicate disease after primary treatment failure. With advanced ablative surgery comes the challenge to find an ideal reconstructive option that will optimize functional outcomes which has shown to be particularly challenging when operating in a post-radiated field with a higher risk for pharyngocutaneous fistulas. The authors present a case where reconstruction of such a defect after local failure with primary chemoradiation was successful using a single stage reconstruction with the gastric pull up technique in combination with a pectoralis major myocutaneous flap. As the risk of anastomotic leak is significantly higher in patients following radiation, this method showed utilizing a prophylactic muscle flap at the time of reconstruction may further bolster the repair and prevent anastomotic leak.