Locoregional Control Rates Research Articles

Six-year follow-up from the weekly-three-weekly study comparing cisplatin once-a-week to once-every-three-weeks as concurrent chemoradiation for locally advanced head and neck squamous cell carcinoma.

6071 Background: In the weekly-3-weekly (W3W) study, cisplatin at 100 mg/m2 once-every-3-weeks led to superior locoregional control compared to cisplatin 30 mg/m2 once-a-week in combination with radical radiation for locally advanced head and neck squamous cell carcinoma (LAHNSCC). We report the updated analysis of the study. Methods: In this phase III open label non-inferiority study conducted between 2013 and 2017, 300 patients with LAHNSCC were randomly assigned to receive cisplatin 100 mg/m2 once-in-3-weeks or cisplatin 30 mg/m2 once-a-week, concurrently with radiation. The primary endpoint was locoregional control. Secondary outcomes included progression free survival (PFS), overall survival (OS), toxicity, and quality of life. Results: As of February 5, 2022 (median follow-up, 77.3 months), 132 patients (44%) have had an event for locoregional recurrence; 75 (50%) in the once-a-week cisplatin arm and 57 (38%) in the once-every-3-weeks cisplatin arm. The updated estimated cumulative 2-year locoregional control rates were 59.3% and 75.3% in the once-a-week and once-every-3-weeks cisplatin arms, respectively; absolute difference, 16% (95% CI, 7.19 to 24.81). The estimated 5-year locoregional control rates were 48.2% and 55.2% in the once-a-week and once-every-3-weeks cisplatin arms respectively; absolute difference, 7% (95% CI, -2.5 to 16.5). The median time to locoregional failure was 46.1 months (95% CI, 31.63 to 60.56) in the once-a-week cisplatin arm, and 57.9 months (95% CI, 47.1 to 68.6) in the once-every-3-weeks cisplatin arm; HR, 1.43 (95% CI, 1.01 to 2.02); P = 0.042. The estimated median PFS was 17.5 months (95% CI, 0 to 38.31) in the once-a-week cisplatin arm, versus 37.5 months (95% CI, 28.45 to 46.45) in the once-every-3-weeks cisplatin arm; HR, 1.13 (95% CI, 0.85 to 1.5); P = 0.41. Events for OS included 173 (57.7%) deaths; 109 (36.3%) patients are alive, and 18 (6%) are lost to follow-up. The 5-year OS in the once-a-week and once-every-3-weeks cisplatin arms were 43.1% and 48.6%, respectively. Estimated median OS was 38.5 months (95% CI, 16.3 to 60.7) in the once-a-week cisplatin arm, versus 57.3 months (95% CI, 38.6 to 75.9) in the once-every-3-weeks cisplatin arm; HR, 1.19 (95% CI, 0.89 to 1.6); P = 0.238. Details regarding chronic toxicities and second primaries will be presented. Conclusions: Long term follow-up confirms that cisplatin at 100 mg/m2 administered once-every-3-weeks concurrently with radical radiation for LAHNSCC leads to superior locoregional control and should remain the standard of care. The study was not powered to test for a difference in OS; OS was numerically higher in the once-every-3-weeks cisplatin arm, but the difference did not attain statistical significance. Clinical trial information: CTRI/2012/10/ 003062.

CCTG BL13 a randomized phase II trial assessing trimodality therapy with or without adjuvant durvalumab to treat patients with muscle-invasive bladder cancer (NCT03768570).

TPS4619 Background: Immunotherapy improves outcomes in the advanced (Bellmunt 2019; Powles 2020) as well as in the adjuvant setting post cystectomy (Bajorin 2021) for muscle invasive bladder cancer (MIBC) patients. Trimodality treatment (TMT) consisting of transurethral resection of bladder tumor (TURBT) followed by chemoradiotherapy (CRT) may be considered an alternative to radical cystectomy in MIBC. The role of radiotherapy and chemotherapy as immune system stimulants provides a rationale to evaluate the anticancer activity of checkpoint inhibitors in this patient population. Durvalumab, an anti PDL1 inhibitor, administered after CRT leads to improvement in PFS and OS in patients with locally advanced NSCLC, which further supports the rationale for this study (Antonia 2017, 2018). We hypothesized that durvalumab will improve outcomes in patients with MIBC when administered in the adjuvant setting after completion of trimodality therapy. Methods: CCTG BL13 is a Canadian Cancer Trials Group, randomized phase II trial in patients with stage T2-T4a N0M0, urothelial carcinoma treated with TURBT followed by radiotherapy with concurrent chemotherapy. Treatment arms consist of durvalumab 1500 mg IV q 4 weeks for 12 months versus surveillance. The primary objective: to compare disease free survival (DFS) between arms (RECIST 1.1, investigator assessed). Secondary endpoints include a non muscle-invasive bladder cancer recurrence rate (< T2); locoregional control rate; overall survival; bladder intact DFS, patterns of disease recurrence; metastasis free survival; safety; quality of life ; economics evaluation. A pilot sub study (BL13F) has been activated and will evaluate the feasibility of electronic real-time patient self-reporting of immunotherapy related symptomatic adverse events using the SYMPTOM-IQ Tool on the uMotif Mobile Health Application (APP). Statistical Design: Randomization 1:1 balanced for stratification factors: ECOG PS; neoadjuvant chemotherapy; radiation field extent; T2 vs T3/T4; centre. Assuming a 2-year DFS rate 65% for patients on the control arm and estimated 12% improvement in the 2-year DFS rate (65% to 77% (HR 0.61)) with 80% power using a 1-sided 10% level test requires a sample size of 190 including 5% drop out rate. Conduct to Date: Study activation Dec 2018. Enrollment as of January 31 2022: 49. The DSMC reviewed and recommended trial continuation in November 2021. Clinical trial information: NCT03768570.

Outcomes of carotid sparing intensity-modulated radiotherapy for early stage glottic cancer in 201 patients: Multicenter study of Turkish Radiation Oncology Society/TROD-01-007.

To assess and report clinical outcomes after carotid sparing intensity-modulated radiotherapy for early stage laryngeal cancer. We retrospectively analyzed 201 patients with early stage glottic laryngeal cancer treated with carotid sparing intensity-modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) techniques in six TROD centers. After a median follow-up of 31 months the actuarial 1- and 3-year local and locoregional control rates were 99.4% and 94.7%, 98.4% and 93%, respectively. T classification, anterior commissure involvement, IMRT technique, and type of fractionation were not found to be prognostic for local control. Overall, eight patients had lost their organ function due to recurrence or toxicity. Grade 3 and 4 acute laryngeal edema was seen in eight (4%) and one (0.5%) of patients, respectively. Grade 3 and 4 late laryngeal edema developed in two (1%) and one patient (0.5%), respectively. Oncologic outcomes of patients treated with carotid sparing IMRT were excellent; comparable with historical series, with acceptable side effects. Longer follow-up is needed to estimate long term effect on stroke.

Clinical presentation and outcome of human papillomavirus-positive nasopharyngeal carcinoma in a North American cohort.

The objective of this study was to describe the clinical presentation and outcomes of human papillomavirus (HPV)-positive nasopharyngeal cancer (NPC) versus Epstein-Barr virus (EBV)-positive NPC and HPV-positive oropharyngeal cancer (OPC). Clinical characteristics and presenting signs/symptoms were compared between patients who had viral-related NPC versus viral-related OPC treated with intensity-modulated radiotherapy from 2005 to 2020 and who were matched 1:1 (by tumor and lymph node categories, smoking, age, sex, histology, and year of diagnosis). Locoregional control (LRC), distant control (DC), and overall survival (OS) were compared using the 2005-2018 cohort to maintain 2 years of minimum follow-up. Multivariable analysis was used to evaluate the cohort effect. Similar to HPV-positive OPC (n = 1531), HPV-positive NPC (n = 29) occurred mostly in White patients compared with EBV-positive NPC (n = 422; 86% vs. 15%; p < .001). Primary tumor volumes were larger in HPV-positive NPC versus EBV-positive NPC (median volume, 51 vs. 23 cm3 ; p = .002), with marginally more Level IB nodal involvement. More patients with HPV-positive NPC complained of local pain (38% vs. 3%; p = .002). The median follow-up for the 2005-2018 cohort was 5.3 years. Patients who had HPV-positive NPC (n = 20) had rates of 3-year LRC (95% vs. 90%; p = .360), DC (75% vs. 87%; p = .188), and OS (84% vs. 89%; p = .311) similar to the rates in those who had EBV-positive NPC (n = 374). Patients who had HPV-positive NPC also had rates of LRC (95% vs. 94%; p = .709) and OS (84% vs. 87%; p = .440) similar to the rates in those who had HPV-positive OPC (n = 1287). The DC rate was lower in patients who had HPV-positive disease (75% vs. 90%; p = .046), but the difference became nonsignificant (p = .220) when the analysis was adjusted for tumor and lymph node categories, smoking, and chemotherapy. HPV-positive NPC and EBV-positive NPC seem to be mutually exclusive diseases. Patients who have HPV-positive NPC have greater local symptom burden and larger primary tumors but have similar outcomes compared with patients who have EBV-positive NPC or HPV-positive OPC.

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.

Could Concurrent Capecitabine with Hypofractionated Radiotherapy in Elderly Patients with Muscle-Invasive Bladder Cancer be an Option?

Background:Repopulation of tumor cells during radiotherapy of transitional cell bladder carcinoma is believed to be a significant cause for treatment failure, and it was reported from clinical observations that the local control rate decreased with a prolonged treatment time, so accelerated hypofractionated radiotherapy with concurrent capecitabine may provide good local control in elderly patients unfit for surgery. The study aimed to evaluate the tolerability and efficacy of hypofractionated radiotherapy with capecitabine in elderly patients with urothelial carcinoma. Methods: Between October 2019 and September 2021, 30 patients with muscle-invasive bladder cancer staged T2-4aN0M0, underwent transurethral resection of bladder tumor followed by capecitabine (825 mg/m2 orally, 2 times a day) and radiation therapy (55 Gy in 2.2 Gy per fraction). Results:Thirty patients with a median age of 73.5 years (range, 65-85) were included in our study. Most patients had T2N0, and T3N0 (28 patients), furthermore 73.3% had an intermediate-grade tumor, Transurethral resection of bladder tumor was incomplete in 43.3. No grade 4 toxicity was documented. Grade 3 urinary toxicities occurred in two patients requiring hospitalization and temporal radiation cessation. Regarding late toxicities, no grade 3 or 4 toxicity was reported. A complete response was obtained in 56.7% of patients. After a median follow-up of 16 months, the locoregional control rate was 63%. Overall survival, local failure-free survival, and event-free survival were 100%, 93.3%, 80% and 43.3%, 33.3%, 30% at one and two years respectively. Conclusion:Hypofractionated chemoradiation with capecitabine, appears to be an effective and well-tolerated curative treatment strategy in the selected elderly population with urothelial carcinoma.

Validation of a prognostic scoring system for postmastectomy locoregional recurrence in breast cancer

BackgroundTo date, it remains unclear which patients with breast cancer (BC) benefit from post-mastectomy radiotherapy (PMRT). Cheng et al. developed and validated a scoring system based on 4 prognostic factors for locoregional recurrence (LRR) to identify patients in need for PMRT. These factors include age, estrogen receptor status, lymphovascular status and number of affected axillary lymph nodes. PurposeTo validate the scoring system for LRR in BC developed by Cheng et al. by using an independent BC database. Methods and materialsWe retrospectively identified 1989 BC cases, treated with mastectomy (ME) with or without PMRT at the University Hospitals Leuven between 2000 and 2007. The primary endpoint was 5-year locoregional control rate with and without PMRT, according to the LRR score. ResultsMedian follow-up time was 11.4 years. After excluding patients with missing variables 1103 patients were classified using the LRR scoring system: 688 (62.38%) patients were at low risk of recurrence (LRR score 0–1), 335 (30.37%) patients were at intermediate risk of recurrence (LRR score 2–3) and 80 (7.25%) patients were at high risk of recurrence (LRR score ≥4). 5-year locoregional control rates with and without PMRT were 99.20% versus 99.21% (p = 0.43) in the low-risk group; 98.24% versus 85.74% (p < 0.0001) in the intermediate-risk group and 96.87% versus 85.71% (p = 0.10) in the high-risk group respectively. ConclusionOur validation of the LRR scoring system suggests it can be used to point out patients that would benefit from PMRT. We recommend further validation of this scoring system by other independent institutions before application in clinical practice.

Radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer in patients with cisplatin-ineligible renal dysfunction: A retrospective study.

Clinical trials have not fully demonstrated the efficacy and safety of radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer (LA-SCCHN) in patients with cisplatin-ineligible renal dysfunction. Patients who received radiotherapy plus cetuximab for LA-SCCHN at Chiba University Hospital (Chiba, Japan) between July 2013 and October 2018 were retrospectively reviewed. Background characteristics and locoregional control and overall survival rates were compared between patients with and without renal dysfunction. Survival was examined using Kaplan-Meier analysis and an adjusted Cox proportional hazards model. Kaplan-Meier analysis demonstrated that overall survival was shorter in patients with creatinine clearance of <45 ml/min (P=0.041; log-rank test). However, there was no difference in the locoregional control rate (P=0.477; log-rank test). Adjusted Cox analysis revealed that the risk of death was increased by 2.52-fold (hazard ratio, 2.52; 95% confidence interval, 1.01-6.30; P=0.048) if creatinine clearance was <45 ml/min. Moderate to severe renal dysfunction did not affect the locoregional control rate in patients with LA-SCCHN treated with radiotherapy plus cetuximab but was an adverse prognostic factor.

Trilynx: A Phase 3 Trial of Xevinapant and Concurrent Chemoradiotherapy (CRT) for Locally Advanced Head and Neck Cancer

Purpose/Objective(s) Concurrent CRT is the standard of care for previously untreated patients with locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Xevinapant (Debio 1143) is an orally available antagonist of inhibitor of apoptosis proteins with the potential to enhance the antitumor activity of platinum-based chemotherapy and radiotherapy. The radiosensitizing effect of xevinapant is mediated through caspase activation and TNF, IFNγ, and CD8 T cell-dependent pathways. Three-year follow-up results from a randomized Phase 2 study showed significant improvements for xevinapant versus placebo in addition to standard CRT for locoregional control (LRC) rate at 18 months, progression-free survival (PFS) and overall survival (OS). The addition of xevinapant was well tolerated, manageable and did not jeopardize backbone therapy [1, 2]. Materials/Methods TrilynX is a multinational, phase 3, double-blind, placebo-controlled, randomized clinical study assessing the efficacy of xevinapant in combination with concurrent CRT compared with placebo in combination with CRT for LA-SCCHN. Adult patients with newly diagnosed, pathologically proven, treatment-naive LA-SCCHN will be enrolled. Study population will include hypopharyngeal, laryngeal and p16-negative oropharyngeal. Other eligibility criteria: ECOG PS 0 or 1, AST and ALT ≤ 3.0 x ULN, total bilirubin ≤ 1.5 × ULN, and eligible for definitive CRT. Approximately 700 eligible patients will be randomly assigned to receive oral xevinapant at 200 mg per day on days 1 to 14 of 3-week cycles or placebo for three cycles in combination with cisplatin (100 mg/m², q3w) for three cycles, and concomitant standard fractionation intensity-modulated radiotherapy (70 Gy/7 weeks). The concurrent CRT period will be followed by a monotherapy period consisting of further three cycles of xevinapant or placebo. The primary endpoint is Event Free Survival (EFS) assessed by a Blinded Independent Radiological Committee (BIRC). An interim analysis will occur when 279 EFS events as assessed by the BIRC are observed. The primary analysis will occur once 429 EFS events are observed. TrilynX has ∼90% power to detect the expected hazard ratio benefit of 0.73. Secondary endpoints include OS, PFS, LRC, objective response rate, health-related quality of life, and safety. Patients will be followed up for a minimum of 60-months. PK sparse sampling will be performed to assess exposure-response relationships with efficacy and safety. Biomarkers of response and resistance will be explored. TrilynX started in August 2020 and is ongoing. Results TBD Conclusion TBD Concurrent CRT is the standard of care for previously untreated patients with locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Xevinapant (Debio 1143) is an orally available antagonist of inhibitor of apoptosis proteins with the potential to enhance the antitumor activity of platinum-based chemotherapy and radiotherapy. The radiosensitizing effect of xevinapant is mediated through caspase activation and TNF, IFNγ, and CD8 T cell-dependent pathways. Three-year follow-up results from a randomized Phase 2 study showed significant improvements for xevinapant versus placebo in addition to standard CRT for locoregional control (LRC) rate at 18 months, progression-free survival (PFS) and overall survival (OS). The addition of xevinapant was well tolerated, manageable and did not jeopardize backbone therapy [1, 2]. TrilynX is a multinational, phase 3, double-blind, placebo-controlled, randomized clinical study assessing the efficacy of xevinapant in combination with concurrent CRT compared with placebo in combination with CRT for LA-SCCHN. Adult patients with newly diagnosed, pathologically proven, treatment-naive LA-SCCHN will be enrolled. Study population will include hypopharyngeal, laryngeal and p16-negative oropharyngeal. Other eligibility criteria: ECOG PS 0 or 1, AST and ALT ≤ 3.0 x ULN, total bilirubin ≤ 1.5 × ULN, and eligible for definitive CRT. Approximately 700 eligible patients will be randomly assigned to receive oral xevinapant at 200 mg per day on days 1 to 14 of 3-week cycles or placebo for three cycles in combination with cisplatin (100 mg/m², q3w) for three cycles, and concomitant standard fractionation intensity-modulated radiotherapy (70 Gy/7 weeks). The concurrent CRT period will be followed by a monotherapy period consisting of further three cycles of xevinapant or placebo. The primary endpoint is Event Free Survival (EFS) assessed by a Blinded Independent Radiological Committee (BIRC). An interim analysis will occur when 279 EFS events as assessed by the BIRC are observed. The primary analysis will occur once 429 EFS events are observed. TrilynX has ∼90% power to detect the expected hazard ratio benefit of 0.73. Secondary endpoints include OS, PFS, LRC, objective response rate, health-related quality of life, and safety. Patients will be followed up for a minimum of 60-months. PK sparse sampling will be performed to assess exposure-response relationships with efficacy and safety. Biomarkers of response and resistance will be explored. TrilynX started in August 2020 and is ongoing. TBD TBD

Analysis of Outcomes by Smoking Status in a Phase III Trial of De-Escalated Adjuvant Chemoradiation Therapy in Human Papillomavirus (HPV(+)) Oropharyngeal Squamous Cell Carcinoma (OPSCC)

<h3>Purpose/Objective(s)</h3> In this study, patients with HPV(+)OPSCC were randomized to de-escalated adjuvant therapy (DART) versus standard of care adjuvant therapy (SOC) and were stratified by smoking < or ≥10 pack-years (pys). We performed a prespecified analysis of oncologic outcomes by treatment arm and smoking history, as patients with any smoking status were trial-eligible. We hypothesized that patients with ≥10 pys smoking history would have similar outcomes to patients with <10 pys. <h3>Materials/Methods</h3> MC1675 inclusion criteria have been previously reported. Smoking history was collected and stratified by < or ≥10 pys. MC1675 had a lead-in safety evaluation whereby the first 10 smokers who were randomized to DART were evaluated for locoregional control with consideration for dose modification pending the locoregional recurrences. Prespecified safety parameters were met and patients with a smoking history were allowed on study. Patients were also stratified on study by extranodal extension (ENE+ vs ENE-). We additionally analyzed outcomes by treatment arm and by ENE+ vs ENE-. Kaplan-Meier curves were constructed for various subgroups and point-estimates for rates of overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) at 2 years were calculated. <h3>Results</h3> In total, 194 patients (mean age 59.4 yrs, SD 8.48; 89.2% male) were enrolled, (randomized 2:1, DART: 130, SOC: 64); 139 patients (72%) smoked <10 pys and 55 patients (28%) ≥10 pys. There was no significant difference in 2-year LRC, PFS, or OS for patients with ≥10 pys vs <10 pys (PFS data in Table 1). For patients receiving DART, there was no significant difference in 2-year PFS for patients with ≥10 pys (<i>n</i> = 37) vs <10 pys (<i>n</i> = 93), 88.2% vs 87.4%, <i>p</i> = 0.31). As previously reported, ENE+ patients receiving DART had worse PFS than those receiving SOC. However, amongst those who were ENE+ and treated with DART, 2-year PFS was not significantly different for ≥10 pys vs <10 pys (PFS 77.4% vs 81.2%, respectively; log-rank, <i>p</i> = 0.17). <h3>Conclusion</h3> Patients with ≥10 pys had similar oncologic outcomes to those with <10 pys. Outcomes for patients treated with DART did not differ by smoking history in this prespecified analysis. These results suggest that smoking status alone does not portend worse outcomes with DART compared to SOC and that selected patients with ≥10 pys should be considered eligible for de-escalation protocols.

Utility of Intermediate Risk Volumes in Human Papilloma Associated Oropharyngeal Cancer: A Pattern of Failure Analysis

<h3>Purpose/Objective(s)</h3> Head/neck radiotherapy contouring guidelines recommend the use of an intermediate risk volume and dose around the primary target in head and neck radiotherapy. Patients with human papilloma virus (HPV) related oropharyngeal squamous cell carcinoma (OPSCC) have locoregional control (LRC) rates that are in excess of 90% with definitive radiotherapy. We hypothesized that intermediate risk volume and doses would have limited utility in these patients. <h3>Materials/Methods</h3> Following institutional review board approval, a database of p16+ and/or HPV OPSCC AJCC Stage I-III patients treated with definitive radiotherapy with or without chemotherapy was queried. Patient with documented locoregional recurrence (LRR) after the end of RT were identified. Diagnostic imaging at recurrence (rDI) was co-registered to the patient's simulation CT (sCT). The recurrence gross tumor volume (rGTV) on the rDI was contoured. In-field failure was defined as ≥95% of the recurrence volume, marginal as 20–95%, and out-of-field as ≤20% lying within the 95% high-dose prescription isodose lines. Patients with marginal or out-of-field recurrences were identified, and the initial treatment GTV was expanded by 1.3 cm to create a PTV intermediate dose (PTV-ID). The coverage of the rGTV by the PTV-ID was assessed, with potential benefit defined as near-total encompassing of the rGTV by the PTV-ID. <h3>Results</h3> A total of 534 patients with a median follow-up of 30 months were available for analysis. Actuarial LRC at 3 years was 91.2%. A total of 57 patients with LRR were identified, of which 41 had available RT treatment plans and recurrence imaging. 25 patients (61%) had in-field recurrences, 6 (14.6%) had marginal recurrences, and 10 (24.3%) had out-of-field recurrences. Of the 10 out-of-field recurrences, 4 were within elective neck volumes, 3 were in un-targeted neck regions, and 3 in areas adjacent to the primary. The combined crude marginal and out of field recurrence rate was 3%. In patients with marginal and out-of-field recurrences, none would have been ≥95% encompassed by the PTV-ID expansion. <h3>Conclusion</h3> In this large retrospective evaluation of an intermediate dose volume for patients with HPV-related OPSCC, we found no potential patients whose recurrences may have been prevented with a PTV-ID. The omission of an intermediate risk volume/dose around the primary or at-risk nodal echelons may be reasonable.

Organ Preservation with Definitive Chemoradiotherapy for T4 Laryngeal Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> Randomized trials established chemoradiotherapy as standard treatment for locoregionally advanced laryngeal cancer, but T4 patients were largely excluded from RTOG 91-11. The standard of care for T4 patients includes upfront surgical resection. Our institution has experience with organ preservation for this population. The purpose of this study was to report T4 laryngeal cancer patient outcomes, including those with T4 disease, treated with chemoradiotherapy. <h3>Materials/Methods</h3> We retrospectively reviewed all T4 larynx patients at our institution who received definitive chemoradiation. From January 2010 to December 2018, patients with T4 larynx were identified. Induction chemotherapy typically consisted of 2 cycles of carboplatin (AUC=6 on d1) and paclitaxel (100 mg/m² on d1/d8/d15). Chemoradiation typically consisted of 4 to 6 alternating weekly cycles of paclitaxel (100 mg/m² on d1), infusion 5-fluorouracil (600 mg/m²/d on d1-5), hydroxyurea (500 mg PO BID), and either 2 Gy daily or 1.5 Gy twice-daily irradiation followed by a 9-day treatment break (TFHX). The Kaplan-Meier method was used to estimate rates of locoregional control (LRC), distant metastasis-free survival (DMFS), overall survival (OS), and laryngectomy free-survival. <h3>Results</h3> 37 patients met eligibility criteria and were included for analysis. Median follow-up was 45.6 months. 84% of patients received induction chemotherapy. 73% of patients were treated using a twice daily approach, while 27% were treated with daily fractionation with a median dose of 73 Gy (IQR: 71-74). Two-year locoregional control (LRC), distant metastasis-free survival (DMFS), overall survival (OS), and laryngectomy-free survival (LFS) was 90%, 85%, 84%, and 90%, respectively. Four-year LRC, DMFS, OS, and LFS was 87%, 84%, 66%, and 90%, respectively. Three patients required laryngectomy for recurrent or persistent disease. Of disease-free patients, none required laryngectomy for intractable dysfunctional larynx. 60% of patients required upfront tracheostomy and 60% required a feeding tube prior to treatment. 100% of patients remained tracheostomy-free if no upfront tracheostomy was placed, while 45% of patients with a tracheostomy upfront were tracheostomy-free 1 year after treatment. 92% of patients remained gastrostomy-tube independent if no gastrostomy-tube was required upfront, while 70% of patients were gastrostomy-tube independent 1 year after treatment if they required a gastrostomy-tube upfront. <h3>Conclusion</h3> Promising laryngectomy free survival is seen with TFHX concurrent chemoradiation for T4 laryngeal patients. T4 disease had outcomes similar to patients with less advanced disease treated on Radiation Therapy Oncology Group 91-11.

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Abstract PD7-04: Avoidance of radiotherapy for low risk early breast cancer using LUMINA Trial criteria and accounting for endocrine therapy adherence

Abstract Objectives: Adjuvant radiotherapy (RT) is a standard component of breast conserving therapy for early stage breast cancer. However, in especially low risk disease, the benefit of radiotherapy may be small. Randomized trials have investigated the feasibility of RT omission in subgroups of patients defined by clinicopathologic variables only. Five biomarker based single arm trials (IDEA, PRECISION, LUMINA, PRIMETIME, EXPERT trials) are ongoing with the goal of using molecular data to refine patient selection for RT omission. This analysis reports on the treatment outcomes of low risk ER positive early stage breast cancer treated with adjuvant RT or RT omission at a multi-hospital health system. Inclusion criteria from LUMINA trial were used to select a very low risk population and subgroup analyses were performed to investigate the influence of endocrine therapy (ET) adherence on outcomes. Methods: The shared electronic health record of multiple facilities within a university health system was queried to identify women with pathologic T1-2 N0 breast cancer treated with breast-conserving surgery between 2007 and 2016. Data collection included demographic features, tumor characteristics, treatment type, endocrine therapy adherence, and locoregional recurrence events. Analysis was restricted to those patients treated with EBRT or RT omission. To identify the low risk patients, inclusion and exclusion criteria from LUMINA trial (age ≥ 55, unifocal, unilateral, ductal, tubular or mucinous histology, T1N0, grade 1-2, ER+ and PR&amp;gt;20 and HER2-, LVI -, margin &amp;gt; 2mm, Ki67 ≤ 13.25, agreed to start endocrine therapy) were applied. Five-year loco-regional control (LRC) rates were compared across groups using the Kaplan-Meier method. Results: 115 patients met LUMINA inclusion criteria. Of these, 84 were treated with EBRT and 31 with RT omission. ET adherence information were available for 101 patients. Patients who completed 5 years of ET or discontinued owing to disease recurrence or death were categorized as ET adherent (ETA) and those who discontinued before 5 years due to other reasons were categorized as ET non-adherent (ETNA). Median ET duration in ETA was 60 months (49-118 months) and in ETNA was 19 months (1-58 months). 5-year LRC rates for RT vs. RT omission were 100 % vs. 94 % (95% CI 82-100). This difference was borderline statistically significant (p = 0.06). On subset analysis, 5-year LRC rates for RT and RT omission were both 100 % in ETA. The 5-year LRC rates for RT vs. RT omission were 100 % vs. 83% (95% CI 54-100) in ETNA (p= 0.18). Conclusion: In this modern series, patients with very low risk early breast cancer selected using criteria from the LUMINA trial exhibited excellent local control with ET alone if they were treatment adherent. This finding awaits validation in large prospective cohorts. By contrast, ET alone may be insufficient in patients likely to be non-adherent to treatment. Notably, prospective trials should closely follow and report ET adherence. Table 1.Patient tumor and treatment characteristicsEBRT (n=84)RT omission (n=31)Age (median)63 (55-76)73 (63-81)Median follow-up (months)53 (8-98)43 (7-70)HistologyDuctal72 (86%)30 (97%)Other12 (14%)1 (3%)StageT1mic2 (2%)0T1a12 (14%)9 (29%)T1b34 (41%)11 (35%)T1c36(43%)11 (35%)GradeG149 (58%)23 (74%)G235 (42%)8 (26%)Endocrine therapy (ET)ET median duration (months)60 (2-118)55 (1-72)ET Adherent60 (71%)17 (55%)ET Non-adherent15 (18%)9 (29%)ET adherence not available9 (11%)5 (16%) Table 2.5-year Loco-regional control ratesRTRT omissionLog-rank test p valueLUMINA All (N=115)100%94%0.06LUMINA ET Adherent (N=77)100%100%LUMINA ET Non-adherent (N=24)100%83%0.18 Citation Format: Seung Won Seol, Lauren Weller, Travis Pflederer, Chelain Goodman, Eric D Donnelly, John P Hayes, Jonathan B Strauss. Avoidance of radiotherapy for low risk early breast cancer using LUMINA Trial criteria and accounting for endocrine therapy adherence [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-04.

Quality of life score as a prognosticator for pharyngeal cancer patients treated with radiotherapy

The purpose of this study was to evaluate the prognostic value of quality of life (QOL) scores acquired not only pre-treatment, but also 1 month after treatment for locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with pharyngeal cancer treated using radiotherapy. Data for 102 patients with naso-, oro-, or hypo-pharyngeal cancer treated between December 2008 and September 2017 were retrospectively analyzed. About 90% of the patients were male. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) was used for QOL assessments. Associations between QLQ-C30 scores before and 1 month after treatment and outcomes including LRC, DMFS, and OS were analyzed using Cox proportional hazard models. Median follow-up was 37 months (range, 5–117 months). Three-year LRC, DMFS, and OS rates were 77.8%, 60.0%, and 66.5%, respectively. Pre-treatment emotional functioning and diarrhea at 1 month after treatment were identified as significant predictors of LRC. Pre-treatment global QOL and diarrhea at 1 month after treatment were detected as significant predictors of DMFS. Pre-treatment emotional functioning, pre-treatment appetite loss, and diarrhea at 1 month after treatment were detected as significant predictors of OS. Diarrhea at 1 month after treatment was the most powerful QOL variable for predicting LRC, DMFS and OS. Our study revealed that several QOL scores not only before treatment but also 1 month after treatment correlated with LRC, DMFS and OS. In particular, the diarrhea domain of QOL at 1 month after treatment offered the most powerful prognosticator for pharyngeal cancer patients treated with radiotherapy.

Postoperative hypofractionated-accelerated radiotherapy (HypoAR) for locally advanced rectal cancer.

despite the advances in preoperative hypofractionated-accelerated radiotherapy for patients with locally advanced rectal cancer, postoperative radiotherapy delivered with standard fractionation (46-50 Gy in 5weeks) remains a standard adjuvant schedule. The role of hypofractionated-accelerated radiotherapy in a postoperative setting remains largely unexplored. eighty-eight patients with rectal cancer infiltrating the rectal wall and/or having metastasis to the perirectal lymph nodes were treated with surgery followed by adjuvant chemotherapy and, subsequently, with hypofractionated-accelerated radiotherapy. Ten fractions of 3.4 Gy were delivered to the pelvis for 10 consecutive fractions, within 12days. The follow-up of patients alive at the time of analysis ranges from 12-120months (median 48). mild abdominal discomfort and diarrhoea were frequent, but medical medication was demanded in 14/88 (15.9%) of patients. The incidence of late toxicities was low; 4/88 (3.5%) patients complained for intermittent intestinal urgency. Locoregional recurrence occurred in 8/88 patients (9%). The 5-year locoregional relapse-free survival was achieved in 89.7% of patients, and this dropped to 84% in node-positive patients (P=0.45). The 5-year disease-specific overall survival was 72.4%. Nodal involvement showed a trend to negatively affect prognosis (5-year overall survival 68.2 vs. 79.6%; P=0.23). postoperative hypofractionated-accelerated radiotherapy has minimal early and late toxicity. The locoregional control and disease-specific survival rates are similar to the expected from conventional postoperative chemoradiotherapy. The 2.5-fold decrease of radiotherapy treatment time, reduction of waiting lists and the lower overall cost of radiotherapy are additional benefits associated with hypofractionated-accelerated radiotherapy.

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.

The dosimetric and clinical advantages of the GTV-CTV-PTV margins reduction by 6 mm in head and neck squamous cell carcinoma: Significant acute and late toxicity reduction

PurposeWe aim to identify the dosimetric and clinical impact of reducing the total GTV-CTV-PTV margins in head-and-neck squamous cell carcinoma (HNSCC) treated with definitive (chemo)radiation. Materials and methodsThe acute and late toxicity and outcomes of 155 consecutive patients treated between February 2017 and March 2019 with GTV-CTV-PTV margins of 9 mm were compared to those of 155 consecutive patients treated with total margin of 15 mm margin, before April 2015. All patients were treated with VMAT with daily-image guidance using CBCT. ResultsReducing the GTV-CTV-PTV by 6 mm resulted in significant reduction of total irradiated volume (PTV-total) by a median of 28.1% and significant reduction of doses to all salivary glands (largest reduction ipsilateral parotid gland; median −9.6 Gy) and constrictor muscle (−6.1 Gy) with subsequent reduction of the incidence of overall acute grade 3 toxicity (47.7% for 9 mm and 66.5% for 15 mm groups, p = 0.001), grade 3 mucositis (18.1% vs. 35.5%, p < 0.001) and feeding tube-dependency at the end of treatment (24.5% vs. 40%, p = 0.005). The incidence of late grade ≥ 2 xerostomia and dysphagia were also significantly lower in the 9 mm group (31.7% vs. 58.6% p < 0.001, and 15.4% vs. 26.7%, p = 0.04). The 2-year rates of loco-regional control, disease-free and overall survival were 78.8% vs.75.8%, 70.9% vs. 64.4%, and 83.8% vs. 67.6%, (p > 0.05, all). ConclusionReduction of the total GTV-CTV-PTV margins from 15 to 9 mm in HNSCC significantly reduced the irradiated volumes and the dose to salivary glands and constrictor muscle with significant reduction of radiation-related toxicity. The loco-regional control rates of both groups were comparable.

Oxaliplatin-based adjuvant chemotherapy rather than fluorouracil-based chemotherapy in rectal cancer is more efficient to decrease distant metastasis and increase survival after preoperative chemoradiotherapy and surgery: a meta-analysis.

The standard treatment of stage II-III rectal cancer is preoperative chemoradiotherapy (CRT), followed by total mesorectal excision (TME). However, the rate of metastasis is still high following this treatment. Therefore, several adjuvant chemotherapy studies have been conducted on reducing subsequent metastases and increasing survival, although there are still no definite conclusions. We searched for published prospective randomized controlled trials comparing adjuvant chemotherapy regimens following standard preoperative CRT and curative surgery in stage II-III rectal cancer. We systematically searched Medline, Embase, and the Cochrane Library for relevant trials done from January 2004 to January 2021. Review Manager (RevMan, version 5.3) was used to analyze the data. We initially searched 1955 studies. We screened and carefully selected four randomized controlled trials with 2897 patients. Compared to the 5-FU-based regimen group, the oxaliplatin-added regimen group attained a higher 3-year locoregional control rate (relative risk [RR] of 0.64, 95% confidence interval [CI], 0.48-0.86; p = 0.003) and 3-year distant metastasis control rate (RR of 0.82, 95% CI, 0.71-0.95; p = 0.007). The oxaliplatin-added regimen group had significantly increased 3-year disease-free survival with a hazard ratio (HR) of 0.85 (95% CI: 0.74-0.97, p = 0.020), but not overall survival (p = 0.740). Grade 3 or higher acute toxicity rates did not differ between the two groups (p = 0.190). The addition of oxaliplatin to adjuvant therapy for stage II-III rectal cancer following preoperative CRT and TME may increase disease-free survival without significant increases in toxicity, but not overall survival.

Evolution in Sinonasal Mucosal Melanoma Management.

Sinonasal mucosal melanoma is a rare and aggressive cancer with poor prognosis. Surgical resection with clear margins, when possible, remains the treatment of choice. Radiation therapy is generally used in the adjuvant setting with improved rates of local control following complete resection. Traditional chemotherapeutic agents do not improve the rates of locoregional control or survival. Immunotherapy has been used with some responders but with overall relatively poor outcomes. These outcomes highlight the need for new agents and more prospective trials in this space. We provide a unique case report of a patient with an advanced sinonasal mucosal melanoma and an overview of the recent literature pertaining to the management of this disease.