High Locoregional Control Rates Research Articles

Role of TORS as De-Escalation Strategy in HPV-Related Oropharyngeal Cancer, What We Need to Know.

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) presents unique challenges and opportunities for treatment, particularly regarding de-escalation strategies to reduce treatment morbidity without compromising oncological outcomes. This paper examines the role of Transoral Robotic Surgery (TORS) as a de-escalation strategy in managing HPV-related OPSCC. We conducted a comprehensive literature review from January 2010 to June 2023, focusing on studies exploring TORS outcomes in patients with HPV-positive OPSCC. These findings highlight TORS's potential to reduce the need for adjuvant therapy, thereby minimizing treatment-related side effects while maintaining high rates of oncological control. TORS offers advantages such as precise tumor resection and the ability to obtain accurate pathological staging, which can guide the tailoring of adjuvant treatments. Some clinical trials provide evidence supporting the use of TORS in specific patient populations. The MC1273 trial demonstrated promising outcomes with lower doses of adjuvant radiotherapy (RT) following TORS, showing high locoregional tumor control rates and favorable survival outcomes with minimal side effects. ECOG 3311 evaluated upfront TORS followed by histopathologically directed adjuvant therapy, revealing good oncological and functional outcomes, particularly in intermediate-risk patients. The SIRS trial emphasized the benefits of upfront surgery with neck dissection followed by de-escalated RT in patients with favorable survival and excellent functional outcomes. At the same time, the PATHOS trial examined the impact of risk-adapted adjuvant treatment on functional outcomes and survival. The ongoing ADEPT trial investigates reduced-dose adjuvant RT, and the DART-HPV study aims to compare standard adjuvant chemoradiotherapy (CRT) with a reduced dose of adjuvant RT in HPV-positive OPSCC patients. These trials collectively underscore the potential of TORS in facilitating treatment de-escalation while maintaining favorable oncological and functional outcomes in selected patients with HPV-related OPSCC. The aim of this scoping review is to discuss the challenges of risk stratification, the importance of HPV status determination, and the implications of smoking on treatment outcomes. It also explores the evolving criteria for adjuvant therapy following TORS, focusing on reducing radiation dosage and volume without compromising treatment efficacy. In conclusion, TORS emerges as a viable upfront treatment option for carefully selected patients with HPV-positive OPSCC, offering a pathway toward treatment de-escalation. However, selecting the optimal candidate for TORS-based de-escalation strategies is crucial to fully leverage the benefits of treatment de-intensification.

Vulvar Carcinoma: Standard of Care and Perspectives.

Treatment of vulvar carcinoma (VC) is challenging. The objectives of this review were to describe for clinicians the epidemiologic and clinical aspects of VC, the standard of care in terms of primary local treatment and systemic therapies, and the recent innovations and perspectives emerging from translational research in immuno-oncology. We conducted a comprehensive review outlying the clinical aspects and biologic background of vulvar cancer, highlighting modern treatment strategies on the basis of a personalized approach. Epidemiologic data showed a recent rise in incidence of VC, attributed to human papillomavirus. Surgery is the mainstay of primary treatment, but multimodal approaches are frequently required in the presence of adverse prognosis histopathologic factors. Chemoradiation is indicated when organ-sparing surgery is not feasible. However, inability to achieve high locoregional control rates in advanced cases and the morbidity associated with local treatments are still key issues. Recent clinical data showed the benefit of individualized strategies combining organ-sparing surgical strategies, less invasive lymph node staging procedures, and refinement in radiotherapy modalities. Among the most important research area, there is a sound rationale for testing modern systemic approaches such as immune checkpoint inhibitors in selected patients with recurrent and/or metastatic tumors. Although no specific data exist for VC, the role of supportive care and post-treatment rehabilitation strategies is also crucial. There are still insufficient studies dedicated to patients with VC. Public health programs for prevention, screening, and early diagnosis are required, and clinical research should be strengthened to provide high-quality clinical evidence and improve patients' oncologic and functional outcomes.

Outcomes among oropharyngeal and oral cavity cancer patients treated with postoperative volumetric modulated arctherapy.

Presently, there are few published reports on postoperative radiation therapy for oropharyngeal and oral cavity cancers treated with IMRT/VMAT technique. This study aimed to assess the oncological outcomes of this population treated with postoperative VMAT in our institution, with a focus on loco-regional patterns of failure. Between 2011 and 2019, 167 patients were included (40% of oropharyngeal cancers, and 60% of oral cavity cancers). The median age was 60 years. There was 64.2% of stage IV cancers. All patients had both T and N surgery. 34% had a R1 margin, 42% had perineural invasion. 72% had a positive neck dissection and 42% extranodal extension (ENE). All patients were treated with VMAT with simultaneous integrated boost with three dose levels: 66Gy in case of R1 margin and/or ENE, 59.4-60Gy on the tumor bed, and 54Gy on the prophylactic areas. Concomittant cisplatin was administrated concomitantly when feasible in case of R1 and/or ENE. The 1- and 2-year loco-regional control rates were 88.6% and 85.6% respectively. Higher tumor stage (T3/T4), the presence of PNI, and time from surgery >45 days were significant predictive factors of worse loco-regional control in multivariate analysis (p=0.02, p=0.04, and p=0.02). There were 17 local recurrences: 11 (64%) were considered as infield, 4 (24%) as marginal, and 2 (12%) as outfield. There were 9 regional recurrences only, 8 (89%) were considered as infield, and 1 (11%) as outfield. The 1- and 2-year disease-free survival (DFS) rates were 78.9% and 71.8% respectively. The 1- and 2-year overall survival (OS) rates were 88.6% and 80% respectively. Higher tumor stage (T3/T4) and the presence of ENE were the two prognostic factors significantly associated with worse DFS and OS in multivariate analysis. Our outcomes for postoperative VMAT for oral cavity and oropharyngeal cancers are encouraging, with high rates of loco-regional control. However, the management of ENE still seems challenging.

Hypo-Fractionated Palliative QUADSHOT Radiotherapy and Concurrent CDDP in Patients with LAHNSCC: Toxicities and Clinical Outcomes

Shorter palliative hypo-fractionated radiotherapy regimens given concurrently with chemotherapy, preferably cisplatin (radiosensitizer), increase response rates with acceptable toxicity, leading to better compliance of patients with locally advanced squamous cell carcinoma of the head and neck (LAHNSCC) in whom late toxicities due to chemoradiotherapy are less relevant. This single institution prospective interventional phase II study was conducted with the goal of achieving high rates of locoregional control with acceptable treatment-related toxicity. In this prospective interventional phase- II study, 60 patients with LAHNSCC (treatment naive), the majority in stage IVB and ECOG PS ≤ 3, were treated with QUAD SHOT RT using the conventional 2D technique (14Gy in 4 fractions on 2 consecutive days twice daily with a 6-hour interval between the two fractions) and concurrent cisplatin (CDDP) at a dose of 6 mg/m2. This treatment was repeated at 4-week intervals for 2 additional cycles if tumor progression did not occur. The Kaplan-Meier method was used to determine survival probability for progression-free survival (PFS) and overall survival (OS). Descriptive statistics with number and percentage were used for each toxicity and tumor response at different time points. A P value of less than 0.05 was considered significant. In our study, all patients received at least one cycle of QUADSHOT chemoradiotherapy (CTRT), while 35 and 18 patients received the 2nd and 3rd QUADSHOT CTRT, respectively. Of the patients who completed the first cycle of QUADSHOT CTRT, 27 (45%) patients had a partial response (PR) and 22 (36.7%) had stable disease (SD). Of the patients who completed the second cycle QUADSHOT CTRT, 77.2% had SD, while 11.4% had PR and 11.4% had PD. After the 3rd QUADSHOT CTRT, 72.2% had SD, while 11.1% had PR and 16.7% had PD. The overall response rate (SD +PR) in our study was 81%, 88.6%, and 83% after the 1st, 2nd, and 3rd QUADSHOT CTRT, respectively. After the 3rd QUADSHOT CTRT, no patient showed grade 4 toxicity. Most patients had grade I/ II toxicities e.g., skin (grade I -83%), mucositis (grade II -50%), salivary gland toxicity (grade II -50%), grade I laryngitis (83.3%). Grade- III oral mucositis and pharyngitis were seen in 27% and 6.7% of patients, respectively. Median OS and PFS were 7.9 months and 6.2 months, respectively. Concurrent chemotherapy acts as a radiosensitizer and provides a synergistic effect when coupled with hypo-fractionated radiation, resulting in more effective control of locoregional disease in locally advanced head and neck tumors with acceptable toxicities. This study is hypothesis-generating and may serve as a basis for developing optimal CTRT regimens for patients with LAHNSCC who are not suitable for curative treatment.

Advances in Nasopharyngeal Carcinoma Treatment: Induction Chemotherapy and Concomitant Radio-Chemotherapy

Squamous cell carcinoma of the nasopharynx is responsible for 0.7% of all malignant tumors worldwide, with the highest incidence in the population of southern China and Southeast Asia. The standard treatment for locally advanced disease consists of a combination of radiotherapy and chemotherapy in different schedules. Among them, induction chemotherapy followed by concomitant radio-chemotherapy has shown in recent years to be a standard therapeutic option with high rates of locoregional control and overall survival. This paper aims to review the current evidence related to treatment with induction chemotherapy and subsequent radio-chemotherapy in nasopharyngeal cancer, its effectiveness, and the technical aspects of its applicability.

Metastatic cutaneous squamous cell carcinoma to the parotid: Adjuvant radiotherapy and treatment outcomes.

Adjuvant radiotherapy is an established component in the management of metastatic cutaneous squamous cell carcinoma (SCC) involving the parotid gland. Radiotherapy technique, dose and volumes are seldom described sufficiently to allow close examination. We report our treatment outcomes and focus on treatment-related factors that affect outcomes in this cohort. We performed a retrospective review of patients with metastatic cutaneous SCCs who underwent parotidectomy with or without ipsilateral neck dissection. All patients received adjuvant radiotherapy. Demographics, clinical data and treatment details were collected from an intuitional electronic database. Individual patient-level radiotherapy technique, volumes and doses were reviewed. Between July 2008 and July 2018, 60 patients met our inclusion criteria. Median follow-up duration was 32.7 months. The mean age was 66.4 years. The majority of patients (49 patients) received full neck irradiation. The 2-year and 5-year loco-regional failure-free survival was 87% (95% confidence interval (CI): 0.74-0.93) and 71% (95% CI: 0.52, 0.83), respectively. The 2-year and 5-year overall survival was 76% (95% CI: 0.62, 0.85) and 60% (95% CI: 0.45, 0.72), respectively. There were 15 cases of loco-regional failures, with 6 cases with dermal involvement. Lymphovascular invasion (LVI) was associated with higher loco-regional failure (hazard ratio: 8.43, 95% CI: 1.85-38.39, P =0.005) and cancer-specific mortality (hazard ratio: 5.40, 95% CI: 1.40-20.87, P=0.015). Treatment technique, intensity-modulated radiation therapy (IMRT) vs 3D conformal radiotherapy (3D CRT), bolus use, perineural invasion (PNI) and surgical margins were not significantly associated with loco-regional failure. We demonstrated high loco-regional control rates with routine use of comprehensive adjuvant radiotherapy. The presence of LVI was identified as a strong predictor for recurrence. Further analysis will help to define optimal radiation dose and techniques.

Pathologic Complete Response and Oncologic Outcomes in Locally Advanced Breast Cancers Treated With Neoadjuvant Radiation Therapy: An Australian Perspective

To assess the degree of pathologic complete response (pCR), postoperative surgical complication rates, and oncological outcomes in women with locally advanced breast cancer or high-risk breast cancers treated with neoadjuvant radiation therapy (NART). This retrospective, multi-institutional review involved 138 clinically staged patients with 140 breast cancers treated with NART between January 2014 and February 2021. Treatments involved sequential neoadjuvant chemotherapy and NART, followed by mastectomy with or without axillary surgery and immediate autologous breast reconstruction. Descriptive statistics were used to assess patient and disease features, treatment regimens, pathologic response, and factors affecting postoperative complications. Kaplan-Meier curves were performed to assess locoregional recurrence-free, distant metastasis-free, and overall survival outcomes. Median age was 47 years (interquartile range, 42-52). The median follow-up was 35.2 months (interquartile range, 17.1-46.5). pCR was achieved in 36.4% (as defined by Chevallier classification) or 42.1% (as defined by Miller-Payne scores) of patients. Greater pCR rates were achieved for HER2+ (73.8%-85.7%) and triple-negative phenotypes (47.6%-57.1%). There were 21 grade 3 surgical complications including 10 grade 3B breast events and 8 grade 3B donor-site events, where surgical reintervention was required. At 3-years' follow-up, the locoregional recurrence-free survival was 98.1%, distant metastasis-free survival was 83.6%, and overall survival was 95.3%%. NART is feasible to facilitate a single-stage mastectomy and immediate autologous breast reconstruction. This study demonstrated comparable rates of postoperative complication to standard of care, and high rates of pCR, which translates to high rates of locoregional control, distant metastasis-free survival, and overall survival.

Pathological Complete Response and Oncological Outcomes in Locally Advanced Breast Cancers Treated with Neoadjuvant Radiotherapy: An Australian Perspective

<h3>Purpose/Objective(s)</h3> To assess the degree of post-operative surgical complication rates, pathological complete response (pCR), and oncological outcomes in women with locally advanced (LABC) or high-risk breast cancers treated with neoadjuvant radiotherapy (NART). The working hypothesis is that treatment sequence reversal with neoadjuvant radiotherapy leads to good tumor response and equivocal oncological outcomes in LABC when compared to standard of care. <h3>Materials/Methods</h3> This retrospective multi-institutional review involved 138 clinically-staged patients with 140 breast cancers treated with NART between January 2014 and February 2021. Treatments involved sequential NACT and NART, followed by mastectomy with or without axillary surgery and immediate breast reconstruction. Descriptive statistics were used to assess patient and disease features, treatment regimens, pathological response and factors affecting post-operative complications. Kaplan-Meier curves were performed to assess locoregional recurrence free, distant metastasis free and overall survival outcomes. <h3>Results</h3> Median age was 47 years (IQR 42–52) with a median BMI of 26 (IQR 24-30). The median follow-up was 35.2 months (IQR 17.1-46.5). pCR was achieved in 36.4% (as defined by Chevallier Classification) or 42.1% (as defined by Miller-Payne scores) of patients. Higher pCR rates were achieved for HER2 (76.2%-85.7%) and triple negative phenotypes (47.6%-57.1%). There were 21 Grade 3 surgical complications including 10 Grade 3B breast events and 8 grade 3B donor-site events, where surgical reintervention was required. At the 3 years mark, the locoregional recurrence free survival was 98.1% (95% CI 94.0-99.4%), distant metastasis free survival was 83.6% (95% CI 75.8-89.1%) and overall survival was 95.3% (95% CI 90.2-97.7%). <h3>Conclusion</h3> NART is feasible to facilitate a single-stage mastectomy and immediate breast reconstruction. This study demonstrated comparable rates of post-operative complication to standard of care, and high rates of pCR which translates to high rates of locoregional control, distant metastasis free survival and overall survival.

A Phase II Study of Volume and Dose De-Intensification Following Transoral Robotic Surgery (TORS) and Neck Dissection for p16+ Oropharyngeal Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> Current efforts to de-intensify adjuvant therapy for patients with p16+ Oropharyngeal Squamous Cell Carcinoma (OPSCC) have focused on dose de-escalation (ECOG 3311) or volume reduction (AVOID trial). We conducted this prospective Phase II single institution study combining volume and dose de-intensification, in patients with pT0-T3 pN0-N2c p16+ OPSCC, with the goal of maintaining high rates of locoregional control (LRC) and reducing treatment-related toxicity. <h3>Materials/Methods</h3> Eligible patients had pT0-T3 N0-N2c p16+ OPSCC (per AJCC 7th Ed), s/p TORS and neck dissection, with < 5 positive lymph nodes, who met standard indications for adjuvant radiotherapy +/- chemotherapy. Adjuvant RT was delivered in 25 fractions over 5 weeks. The primary site was spared in patients with pT1-T2 tumors resected with negative margins and no LVI or PNI, as per the AVOID trial. If RT to the primary operative bed was indicated, patients received 50, 52.5, or 55 Gy for negative, close, or positive margins, respectively. The neck level(s) with confirmed pathologic disease received 50 Gy, and areas of minor or macroscopic ENE were boosted to 52.5 or 55 Gy, respectively. Other at-risk ipsilateral nodal regions received 45 Gy. The treated volume of the contralateral neck was reduced to mirror the pathologically involved nodal levels in the ipsilateral neck, and received 45 Gy. Concurrent chemotherapy was according to guidelines, but could be omitted in patients with ENE ≤ 1 mm. The trial was powered to demonstrate 2-year LRC rate > 90%. <h3>Results</h3> 118 patients were enrolled between October 2018 and July 2021. Patient characteristics are detailed in the Table. Median follow up is 23 months (range 6 - 40 months). One patient developed regional recurrence after developing distant metastases (DM). No other patients had locoregional failure (LRF), yielding an estimated 2-year LRC rate of 98.8% (95% CI, 92-99.8%). Eight patients (7%) developed DM, and one patient has died of metastatic disease. The TORS resection bed was spared in 55% of patients; due to proximity to level 2, the median dose to the operative bed in these cases was 32.5 Gy (range 16.5 – 46 Gy). Twenty patients had ENE > 1 mm (considered "high risk" per ECOG 3311) and none had LRF. At one-year post-RT, the median MDASI-HN "difficulty swallowing/chewing at its worst" score was 2 (IQR, 1-3), and "choking/coughing with swallowing at its worst" score was 1 (IQR, 0-3), on a scale from 0 (not present) to 10 (as bad as you can imagine). <h3>Conclusion</h3> The combination of adjuvant RT dose de-intensification over 5 weeks and volume reduction, with omission of the primary site in appropriate patients, and reducing the volume of the treated contralateral neck, appears safe. Additional follow up is warranted and ongoing.

HPV-Associated Squamous Cell Carcinomas of the Oropharynx Treated with Curative Intent Radiotherapy: Patterns of Failure Analysis Using a Deformable Registration Methodology

<h3>Purpose/Objective(s)</h3> Although human papillomavirus (HPV)-associated squamous cell carcinomas of the oropharynx (SCCOP) have high locoregional control rates, understanding spatial patterns of recurrence remains important in the IMRT era. A standardized methodology, using deformable registration, has been proposed to more accurately assess recurrent disease volumes in the context of initial treatment dose distributions. In this study we used this methodology to analyze recurrent malignancies in HPV-associated SCCOP. <h3>Materials/Methods</h3> A single institution database was retrospectively assessed for p16 (+) SCCOP treated with curative intent, either definitively or adjuvantly, using IMRT. Recurrence required either pathologic confirmation or clinically conclusive imaging. The earliest image indicative of recurrence was identified (either CT, MRI or PET-CT) and a "recurrent GTV" (rGTV) was contoured. Local and regional recurrences in the same patient were analyzed separately. This image was deformed onto the initial CT simulation, and the deformed rGTV was categorized into five types (A-E). In Types A/B the rGTV centroid was inside the prescribed high dose distribution, and delineated "A" if the dose to 95% of the failure volume (fD95%) was ≥ 95%, versus "B" if < 95%. In Types C/D the rGTV centroid was inside the elective dose distribution, and delineated "C" if fD95% was ≥ 95%, versus "D" if < 95%. In Type E the rGTV centroid was outside the elective and high dose volume. All deformable registrations were performed using MIM treatment planning software. <h3>Results</h3> A total of 140 patients met inclusion criteria, of which 114 were treated definitively and 26 were treated adjuvantly. 17 locoregional recurrences in 16 patients were identified; 8 failed at the primary, 7 failed regionally, and 1 failed both at the primary and regionally. Recurrence was confirmed by pathology in 14 patients. Five patients were AJCC 8^th Stage I, three were Stage II, and eight were Stage III. The mean rGTV was 9.2 cc (0.1 to 60.7). Of the 17 recurrences, 11 (65%) were Type A, two (12%) were Type B, one (6%) was Type C, and three (18%) were Type E. The only Type C recurrence occurred in a patient treated on the radiotherapy alone arm on NRG HN002 within the 48 Gy elective nodal volume. Type E failures occurred in level VI-A in a Stage II base of tongue malignancy, the contralateral neck in a patient treated ipsilaterally for a Stage I tonsillar malignancy, and the base of skull in a Stage III tonsillar malignancy. <h3>Conclusion</h3> In HPV-associated SCCOP locoregional recurrences occur primarily within the high dose volume, indicating a need for improved stratification and potential intensification in a small subset of patients. Deformable registration-based patterns of failure analysis are feasible, and should be the standard reporting methodology.

Adult Head and Neck Rhabdomyosarcoma: Management, Outcomes, and the Effect of Intensity Modulated Radiation Therapy on Locoregional Control

PurposeOnly 9% of adult rhabdomyosarcomas (RMS) present with primary disease in the head and neck (HNRMS). Management is often extrapolated from the pediatric experience in which prognosis is better but treatment imperatives differ. We report management and outcomes of adult HNRMS treated over 3 decades. Methods and MaterialsAdult HNRMS treated from 1984 to 2017 were reviewed. HNRMS were categorized as embryonal/alveolar (E/A) or pleomorphic (P). Standard management was as follows: E/A-HNRMS were treated with neoadjuvant chemotherapy, definitive chemoradiotherapy (CRT), and then maintenance chemotherapy. P-HNRMS were generally treated with surgery +/– radiation. Intensity modulated radiation therapy (IMRT) was adopted from 2005 onward. ResultsFifty-eight patients were eligible; the median age was 32 years. Seventy-six percent of tumors (n = 45) were parameningeal and 45% (n = 26) were >5 cm. Of 45 patients with M0 HNRMS treated with curative intent, 33 (73%) were E/A-HNRMS and 12 (27%) P-HNRMS. Patients with E/A-HNRMS received definitive RT with 66 to 70 Gy in 2 Gy per fraction. Elective nodal RT was routinely delivered. In the pre-IMRT era (before 2005), 12 of 23 (52%) patients with M0 E/A-HNRMS experienced locoregional recurrences. In the IMRT era (2005 and onward), 1 of 10 patients (10%) with M0 disease recurred locally; this patient achieved a complete clinical response despite a 3-week interruption after 48 Gy because of local toxicity but experienced an in-field local recurrence 45 months later that resulted in death. Locoregional control was superior in the IMRT era vs pre-IMRT era (P = .049). Distant metastasis among patients with E/A-HNRMS was the predominant mode of treatment failure (n = 17 of 33, 52%). ConclusionsOur study shows a high rate of locoregional control for adult E/A-HNRMS following definitive CRT using IMRT, and CRT should be considered for the majority of patients in this population. In contrast, P-HNRMS is distinct and requires surgery +/– RT.

Radio(chemo)therapy in anaplastic thyroid cancer—high locoregional but low distant control rates—a monocentric analysis of a tertiary referral center

BackgroundAnaplastic thyroid cancer (ATC) is a lethal disease with highly aggressive disease progression. This study analyses the influence of radio(chemo)therapy, R(C)T, on disease control, survival rates and predictors for survival.Patients and methodsA total of 33 patients with ATC, treated at a tertiary referral center between May 2001 and April 2020 were included. Univariate and multivariate analysis were used to investigate correlates of R(C)T and predictors on disease control and survival rates.ResultsMedian follow-up was 4 months. In UICC stage IVA and IVB median overall survival (OS) was 8 months, median progression-free survival (PFS) was 6 months. Patients with UICC stage IVA and IVB and patients being irradiated with a radiation dose of more than 60 Gy showed increased OS. Of these patients, 3 were alive and free from disease. All of them receiving cisplatin-based radiochemotherapy and a minimum radiation dose of 66 Gy. UICC stage IVC showed a median OS of 2.5 months and a median PFS of 1 month. Only 2 of 16 patients had local failure.ConclusionDepending on UICC stage, RT with high radiation dose can lead to improved OS or at least higher locoregional control. A limiting factor is the high incidence of distant metastases; therefore modern systemic treatment options should be integrated into multimodal therapy concepts.

Phase I Study of Accelerated Hypofractionated Proton Therapy and Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer

Our purpose was to evaluate the maximum tolerated dose of hypofractionated proton beam radiation therapy with concurrent weekly carboplatin/paclitaxel in patients with stage II-III non-small cell lung cancer. A phase I trial was designed using the time-to-event continuous reassessment method. Maximum tolerated dose was defined as the dose associated with a 20% probability of Common Terminology Criteria for Adverse Events protocol-specified serious adverse events (SAEs). Starting dose was 3.5 Gy/fx for 15 fractions with 2 potential escalation and de-escalation levels in 0.25 Gy/fx increments. Chemotherapy was weekly concurrent carboplatin/paclitaxel with 2 cycles of optional consolidation carboplatin/paclitaxel. From May 2015 to September 2016, 23 patients enrolled at a single institution. Of 20 evaluable, median age was 66.5 years (range, 54-89) and 12 were male (60%). Fourteen (70%) had squamous cell and 15 (75%) were stage IIIA. Nineteen (95%) completed all 3 cycles of concurrent chemotherapy, and 16 (80%) received at least 1 cycle of consolidation chemotherapy. Within the 6-month time-to-event continuous reassessment method assessment window, no SAEs were reported, and most patients were treated at the highest dose level. Dose level assignment was 52.5 Gy (n=2), 56.25 Gy (n=4), and 60 Gy (n=14). The posterior probability of dose-limiting toxicity for 60 Gy was 5.3% (95% confidence interval, 1%-18.1%). Acute, nonserious AEs included grade 2 esophagitis in 7 patients (35%) and grade 2 pneumonitis in 1 patient (5%). At a median follow-up of 20.3 months for all and 44.9 months for living patients, there were no grade 4 or 5 AEs, though there were 3 (21% at 24 months) SAEs outside of the dose-escalation window. The 2-year overall survival, local, regional, and distant control rates were 48%, 84%, 77%, and 79%, respectively. Hypofractionated proton beam radiation therapy and chemotherapy up to 60 Gy in 15 fractions is acutely well tolerated, with high rates of locoregional control and overall survival, though late SAEs were noted.

Reduction of Elective Radiotherapy Treatment Volume in Definitive Treatment of Locally Advanced Head and Neck Cancer-Comparison of a Prospective Trial with a Revised Simulated Contouring Approach.

Definitive radiochemotherapy of locally advanced head and neck squamous cell cancer (HNSCC) achieves high locoregional tumor control rates; but is frequently associated with long-term toxicity. A future direction could be a de-escalation strategy focusing on treated volume rather than radiotherapy dose. This analysis evaluates radiotherapy dose and volume parameters of patients treated with a standard contouring approach in a clinical trial context compared with a revised volume-reduced contouring approach. In this case, 30 consecutive patients from the CheckRad-CD8 trial treated at a single study center were included in this analysis. Treatment toxicity and quality of life were assessed at the end of radiotherapy. Standard treatment plans (ST) following state of the art contouring guidelines that were used for patient treatment and volume reduced treatment plans (VRT) according to a revised simulated approach were calculated for each patient. Planning target volumes (PTV) and mean doses to 38 organs-at-risk structures were compared. At the end of radiotherapy patients reported high rates of mucositis; dysphagia and xerostomia. In addition; patient reported quality of life as assessed by the EORTC QLQ-HN35 questionnaire deteriorated. Comparing the two contouring approaches; the elective PTV_56 Gy and the high risk PTV_63 Gy (shrinking field) were significantly smaller in the VRT group. Significant reduction of mean dose to structures of the oral cavity; the larynx as well as part of the swallowing muscles and the submandibular glands was achieved in the simulated VRT-plan. Treatment de-intensification by reduction of the irradiated volume could potentially reduce treatment volume and mean doses to organs at risk. The proposed contouring approach should be studied further in the context of a clinical trial.

High-grade salivary gland cancer: is surgery followed by radiotherapy an adequate treatment to reach tumor control? Results from a tertiary referral centre focussing on incidence and management of distant metastases

PurposeSalivary Gland cancer (SGC) is a rare and heterogenous group of tumors. Standard therapeutic options achieve high local but poor distant control rates, especially in high-grade SGC. The aim of this monocentric study was to evaluate patterns of recurrence and its treatment options (local ablative vs. systemic) in a homogenously treated patient population with high-grade SGC after surgery and radio(chemo)therapy.MethodsMonocentric, retrospective study of patients with newly diagnosed high-grade salivary gland cancer. We retrospectively reviewed clinical reports from 69 patients with high-grade salivary gland cancer in a single-center audit. Survival rates were calculated using the Kaplan–Meier method and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox regression analysis).ResultsThe median time of follow-up was 31 months. After 5 years, the cumulative overall survival was 65.2%, cumulative incidence of local recurrence was 7.2%, whereas the cumulative incidence of distant metastases was 43.5% after 5 years. 30 of 69 patients developed distant metastases during the time of follow-up, especially patients with adenoid cystic carcinoma, salivary duct carcinoma, adenocarcinoma NOS and acinic cell carcinoma with high-grade transformation. The most common type of therapy therefore was chemotherapy (50%). 85.7% of patients with local ablative therapy of distant metastases show disease progression during follow-up afterwards.ConclusionWith surgery and radio-chemotherapy, a high rate of loco-regional control is reached, but over 40% of patients develop distant metastases in the further follow-up which usually present a diffuse pattern involving in a diffuse metastases. Therefore, in the future, intensified interdisciplinary combination therapies even in the first-line treatment in certain subtypes of high-grade SGC should be investigated.

Treatment of patients with locally advanced Merkel cell carcinoma: A multicenter study.

e21566 Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a high risk of recurrence and poor prognosis. The treatment of locally advanced disease includes surgery (SUR) and radiotherapy (RTH) to achieve high locoregional control rates. The sentinel lymph node biopsy (SLNB) is recommended procedure in cases without clinical nodal involvement. In selected cases, chemotherapy (CHT) may also be considered, but its role is not confirmed. This study aimed to analyze outcomes for locally advanced MCC pts treated in routine clinical practice. Methods: We conducted the retrospective analysis of data from 156 MCC pts treated with curative surgery in four oncological centers, diagnosed between 01/2010 and 12/2019, with data cut-off on 31/12/2020. The data collected included epidemiological and clinical information. Survival analyses were performed using the Kaplan-Meier method, log-rank test and multivariate Cox regression. Results: The median patient age at diagnosis was 72 years (30-94); 50.6% were male. The primary tumor (PT) locations were lower limbs (33.3%), upper limbs (30.1%), and head and neck (28.2%). MCC with no PT was diagnosed in 3.9%. In 62.0% the PT was located in the sun-exposed skin. The median tumor size was 25 mm (4-170). Lymph node (LN) involvement (clinical or positive SLNB or LND) at diagnosis was found in 26.9% (n = 42). The scar excision was done in 50.0% (positive in 16.6%), SLNB in 36.5% (positive in 10.5 %), 51.9% of pts received perioperative treatment, including RTH- 86.4%, CHT- 21%. The relapse rate was 38.3% (35.8% local-regional, 11.1% distant). With the median follow-up of 2.2-years, the median disease-free survival (DFS), local relapse-free survival (LRFS), and distant metastases-free survival (DMFS) were not reached. The 1-year DFS, LRFS and DMFS rates were 65%, 68%, and 90%. The negative independent risk factors for DFS were male gender (HR 1.42, 95%CI 1.06-3.01), metastases in LN at diagnosis (HR 5.41, 95%CI 2.39-12.26), no SLNB in pts with no clinical metastases in LN (HR 5.45, 95%CI 2.41-12.3), and no perioperative RTH (HR 2.19, 95%CI 1.29-3.76). The median overall survival (OS) was 6.9 years (95%CI 4.64-9.15). The negative independent risk factors for OS were male gender (HR 1.95, 95%CI 1.16-3.27), age above 70 (HR 2.0, 95%CI 1.15-3.48), metastases in LN at diagnosis (HR 3.15, 95%CI 1.49-6.68), and no SLNB in pts with no clinical metastases in LN (HR 2.30, 95%CI 1.10-4.82). PT location, UV-exposure, and perioperative CHT or RTH were not independent risk factors for OS. Conclusions: Our results confirm that the MCC treatment should be done in an experienced multidisciplinary team. Male gender, nodal involvement at diagnosis, and no SLNB in pts without clinical metastases in LN are associated with poor prognosis in DFS and OS. The perioperative RTH improves the treatment outcomes and reduces disease progression risk but does not impact OS. Perioperative CHT does not affect pts survival.

Anaplastic thyroid cancer: outcomes of trimodal therapy.

BackroundThe purpose of this study is to assess the impact of trimodal therapy [surgery, chemotherapy and external beam radiotherapy (EBRT)] in patients with anaplastic thyroid cancer (ATC) treated with curative intent.Materials and methodsRetrospective review of patients with ATC treated at a tertiary referral centre between January 2009 and June 2020. Data were collected regarding demographics, histology, staging, treatment and outcomes.ResultsSeven patients (4 female) were identified. Median age was 58 years (range 52–83 years). All patients received EBRT with concurrent doxorubicin. Six patients received surgery followed by chemoradiotherapy (CRT), and one underwent neoadjuvant CRT followed by surgery. Median radiological tumour size was 50mm (range 40–90 mm). Six patients had gross extrathyroidal extension and three had N1b disease. Prescribed radiotherapy schedules were 46.4 Gy in 29 bidaily fractions (n = 2, treated 2010), 60 Gy in 30 daily fractions (n = 2), 66 Gy in 30 fractions (n = 2) and 70 Gy in 35 fractions (n = 1; patient received neoadjuvant CRT). CRT was discontinued early for two patients due to toxicities. At median follow up of 5.8 months, 42.9% (3/7) patients were alive and disease-free. Only one patient developed a local failure. Three patients died from distant metastases without locoregional recurrence.ConclusionsDespite poor prognosis of ATC, selected patients with operable tumours may achieve high locoregional control rates with trimodal therapy, with possibility of long-term survival in select cases.

Treatment of Early Stage High-Risk Endometrioid-Type Endometrial Cancer and Patterns of Disease Relapse: A Retrospective Analysis

PurposeA recently published randomized controlled trial has demonstrated that in patients with endometrial cancer with high-risk features, the addition of chemotherapy to radiation therapy, compared with radiation therapy alone, resulted in a significant improvement in failure-free survival. However, in the study, the effect of chemotherapy was limited to stage III patients, and the benefit was less pronounced in stage I and II patients. Our study aims to investigate the current practice of treatment and clinical outcomes in stage I high-risk endometrioid-type endometrial cancer. Methods and MaterialsA single-center retrospective study was conducted on patients with stage I high-risk endometrioid-type endometrial cancer without serous or clear cell features who have undergone hysterectomy between 1998 and 2015. Data on patients, tumor, and treatments were collected and correlated with clinical outcomes. ResultsA total of 1,572 patients with stage I disease were identified and 46 patients who met the inclusion criteria were selected for final analysis. The median age at diagnosis was 63 years (range, 49-86 years) and median follow-up was 5.9 years. Among the entire cohort, 40 (87.0%) patients underwent adjuvant radiation therapy, of which 36 (78.2%) patients underwent external beam radiation therapy and 4 (8.7%) patients underwent vaginal brachytherapy. Two of the 40 patients who received adjuvant radiation therapy also received adjuvant chemotherapy. Six (13.0%) patients received no adjuvant treatment. Of the 46 patients, the cumulative risk of distant recurrence was 19.6%, and only 1 patient (2.2%) recurred within pelvis (perirectal lymph node). Five-year disease-free survival and overall survival rates were 73.1% and 80.1%, respectively. ConclusionsAdjuvant radiation therapy in stage I endometrioid-type endometrial cancer patients with high-risk features resulted in high rates of locoregional disease control, and most recurrences occurred at distant sites. Effective systemic therapy may be indicated in this patient population to further reduce the risk of distant relapses and improve survival.

Accelerated Hyperfractionated Radiotherapy versus Conventional Fractionation Radiotherapy for Head and Neck Cancer: A Meta-Analysis of Randomized Controlled Trials.

Objective The benefits of accelerated hyperfractionated radiotherapy (HART) and conventional fractionation radiotherapy (CFRT) in the treatment of head and neck cancer (HNC) remain controversial. In this study, we analyzed the therapeutic effects of these two treatment regimens to explore whether HART can improve the overall survival (OS) rate and locoregional control (LRC) rate in patients with HNC. Methods The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for eligible studies. The OS rate and LRC rate were considered as the efficacy outcomes. I2 was used to test the heterogeneity among studies with a cutoff value of 50%. Potential publication bias was assessed by funnel plots and Egger's test. We also performed a sensitivity analysis to assess the stability of the results. In this meta-analysis, all analyses were performed using R 3.5.3 software. Results Twelve qualified articles including a total of 2,935 patients were identified. HART had a significant beneficial effect on OS rate (HR = 0.80, 95% CI: 0.65–0.98). Compared with CFRT, HART demonstrated a significantly higher LRC rate (HR = 0.82, 95% CI: 0.71–0.96). Conclusion Our meta-analysis showed that HART can significantly improve OS and LRC compared with CFRT in patients with HNC.

1143P - Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC)

BackgroundCurrent treatment of locoregionally advanced NPC (LRA-NPC) is CCRT with or without adjuvant chemotherapy (CT). The value of adding IC to CCRT in LRA-NPC is unclear. We retrospectively evaluated LRA-NPC patients treated with IC followed by CCRT in a single tertiary center in Turkey. MethodsBetween 2004 and 2016, 202 patients with nonmetastatic LRA-NPC (stage 3-4), 144 males and 58 females ranging from 17 to 75 (median 49) years old, were treated with IC followed by CCRT. Eleven (%5.4) patients had keratinised (WHO I), and 191 (%94.6) had nonkeratinised or undiffrentiated (WHO II-III) carcinoma. Cumulative radiation dose to primary tumor ranged from 60 to 74 (median 70) Gy. Ninety-one (%45) of the patients received 2-dimensional and 111 (%55) received intensity modulated radiotherapy (IMRT). IC consisted of taxane (T)(75mg/ m2) and platinum (P)(75mg/m2) combination (199 patients) or P and fluorouracil or epirubicine (3 patients) combination and 188 of the patients received 3 cycles of IC. Concomittant P was used either weekly (40mg/m2, 25 patients) or every 3-weekly (100mg/m2, 177 patients) application. Follow-up ranged from 5 to 167 months (median, 72.5 months).Table: 1143PTable: 1143PPatient and treatment characteristicsn ( % )StageIII IVA IVB149 (73.7%) 30 (14.9%) 23 (11.4%)Number of induction courses2 3 410 (5%) 188 (93.1%) 4 (2%)Concomittant typeEvery 3 weeks (100mg/m2) Every week (40mg/m2)177 (87.6%) 25 (12.4%)RT technique2-dimensional Intensity modulated91 (45%) 111 (55%)Radiation dose to primary (Gy)≤ 70 > 708 (4%) 194 (96%) ResultsTreatment failure was observed in 52 (%25.7) of the patients (21 local, 13 regional and 27 distant). Distant failure rate of all the patients exceeds 13%. Five and 10 years disease free survival (DFS) rates are 75.2% and 70.4% and overall survival (OS) rates are 78.9% and 64% respectively. In univariate analysis patient age favoring those below 49 and stage of disease favoring WHO II-III were all significant predictors of DFS and OS. In addition pathology was a significant predictor of DFS. ConclusionsLRA-NPC patients treated with IC followed by CCRT have a high locoregional control (LRC) rate. Despite the use of IC distant control remains insufficient and continues to be a challenge in NPC. Besides improving LRC, more effective systemic therapy is needed. Legal entity responsible for the studyMusa Altun, MD. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.