Local-regional Control Rates Research Articles

Clinical Outcomes of Patients With pT1-T2N0 Oral Tongue Squamous Cell Carcinoma.

The objective of this study was to evaluate the clinical outcomes in a cohort of patients with early-stage oral tongue squamous cell carcinoma (OTSCC). We conducted a retrospective analysis of patients with pT1-T2N0 (American Joint Committee on Cancer [AJCC] seventh edition) OTSCC treated from 2000 to 2018. Two-year actuarial rates of local regional control, cancer-specific survival, and overall survival were calculated for the entire cohort and patients with/without adjuvant radiation. Ninety-six patients met the criteria with a median follow-up of 4 years; 14 had adjuvant radiation, while 82 had surgery alone. Two-year local regional control was 82.7% (75.4% to 90.8%) for the entire cohort, 84.9% (77.8% to 93.2%) for surgery only, and 70.7% (50.2% to 99.6%) for patients with adjuvant radiation. Two-year progression-free survival was 82.7% (75.3% to 90.8%). Of the 20 patients with recurrence, 11 (55%) were successfully salvaged. Local regional recurrence remains modest in early-stage OTSCC, but salvage is possible with high survival rates. Level III-retrospective cohort study.

Impact of p53, HIF1a, Ki-67, CA-9, and GLUT1 Expression on Treatment Outcomes in Locally Advanced Cervical Cancer Patients Treated With Definitive Chemoradiation Therapy

The objective of this study was to assess the association between pretreatment p53, hypoxia inducible factor 1a (HIF1a), Ki-67, carbonic anhydrase-9 (CA-9), and glucose transporter 1 (GLUT1) expression in locally advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), local-regional control (LC), and distant metastases-free survival (DMFS). Twenty-eight patients treated definitively and consecutively for cervical cancer with CRT had p53, HIF1a, Ki-67, CA-9, and GLUT1 protein expression assessed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes. Outcomes were stratified by p53 (H-score: <15 vs. ≥15), HIF1a (H-score: <95 vs. ≥95), Ki-67 (labeling index <41% vs. ≥41%), CA-9 (H-score: <15 vs. ≥15), and GLUT1 (H-score: <175 vs. ≥175) expression. OS, PFS, LC, and DMFS rates were calculated using the Kaplan-Meier method, and differences between groups were evaluated by the log-rank test. Notable clinical characteristics of the cohort included median age of 51 years (range: 32 to 74 y), FIGO stage IIB disease (57.2%), clinical node-negative disease (64.3%), squamous cell carcinoma (89.3%), and adenocarcinoma (10.7%). Treatment outcomes included 5-year OS (57.2%), PFS (48.1%), LC (72.1%), and DMFS (62.9%). For HIF1a H-score <95 and ≥95, the 5-year OS (52.0% and 68.4%, P=0.58), PFS (53.0% and 40.9%, P=0.75), LC (71.6% and 68.2%, P=0.92), and DMFS (59.7% and 52.0%, P=0.91) were not significantly different. For Ki-67 labeling index <41% and ≥41%, the 5-year OS (44.9% and 66.6%, P=0.35), PFS (38.9% and 55.4%, P=0.53), LC (57.7% and 85.7%, P=0.22), and DMFS (67.3% and 61.0%, P=0.94) were not significantly different. For CA-9 H-score <15 and ≥15, the 5-year OS (54.4% and 66.7%, P=0.39), PFS (57.3% and 40.0%, P=0.87), LC (70.0% and 70.0%, P=0.95), and DMFS (70.0% and 46.7%, P=0.94) were not significantly different. For GLUT1 H-score <175 and ≥175, the 5-year OS (43.6% and 43.6%, P=0.32), PFS (55.6% and 49.5%, P=0.72), LC (72.9% and 71.5%, P=0.97), and DMFS (62.5% and 59.6%, P=0.76) were not significantly different. For p53, H-score <15 and ≥15, the 5-year OS (62% and 53%), PFS (63% and 30.3%), LC (87.5% and 52%), and DMFS (79.6% and 41.6%). In this study population, HIF1a, Ki-67, CA-9, and GLUT1 expression did not predict treatment response or outcomes in locally advanced cervical cancer patients treated definitively with CRT. There was a nonstatistically significant trend towards worse outcomes with p53 expression.

Impact of IMRT- and VMAT technologies on selection of total dose of radiation therapy in patients with squamous cell carcinoma of anal canal

Accurate determination of the tumor with the use of modern diagnostic methods which make the maximum exposure to the tumor and the identified affected lymph nodes possible lead to careful attitude to healthy tissues and critical structures. During the period 2000-2015 301 patients with squamous cell carcinoma of the anal canal stage T1-4N0-3M0-1 completed complex treatment which consisted of radiation therapy in a conventional or conformal mode, including the use of modern technologies - radiation therapy with intensity modulation - IMRT and arch volume-modulated radiation therapy - VMAT. The use of IMRT andVMAT in comparison with conformal radiation therapy allowed to reduce the frequency of unplanned interruptions up to 48 % (p = 0.005), which led to increase in 5-year rates of local regional control - 83.7 % compared with the group where the interruption was applied - 74.2 % (p = 0.049); also increased the frequency of complete responses in the range of the total dose of 50-54 Gy to 28.5 %, 56-58 Gy to 44.3 % and 60-64 Gy to 26.1 %. The achievement of a complete response led to a significant increase in the 92.1 % 5-year locoregional control compared to the group with the absence of a complete response - 76.5 % (p = 0.001). Modern conservative treatment is based on continuous radiation exposure with the absence of intervals between courses, which is the radiobiologically considered the most effective treatment regimen.

Outcomes Of Carotid Sparing Radiotherapy For Early Stage Glottic Cancer: Turkish Society For Radiation Oncology Group (TROD) Retrospective Study

To report clinical outcomes after on carotid-sparing intensity modulated radiotherapy for early stage laryngeal cancer. We retrospectively analyzed disease, and treatment characteristics for 201 patients with early-stage glottic laryngeal cancer treated in 6 TROD centers between 2012-2019. Using AJCC 8th., TNM staging system, 28 (14%) patients were classified as Tis, 153 (76%) as T1 and 20 (10%) as T2. Dosimetric parameters and local-regional control results of patients treated with carotid sparing IMRT / VMAT (Intensity-modulated radiation therapy / volumetric modulated arc therapy) techniques were evaluated. Median follow-up time was 31 (6-88) months. Median age was 64 (range 39-87) and 188 (93.5%) of the cases were male and 13 (6.5%) female. Anterior commissure involvement was detected in 47 (23.4%) cases. A total of 174 (87%) cases were treated with VMAT and 27 (13%) with IMRT. Total dose ranged from 63 to 70 Gy (median 66Gy) in 28 to 35 fractions using 2 to 2.25 Gy (Median: 2.25 Gy) daily fractions. Local recurrence was detected in six patients (3%), regional recurrence in 3 patients (1.5%), and local and regional recurrence in 1 patient (0.5%). The actuarial 1- and 3-year local control rates were 99.4% and 94.7%, respectively. The actuarial 1 and 3 year local-regional control rates were 98.4% and 93%. Five of seven local recurrences were observed in patients treated with hypofractionation. Stage, anterior commissure involvement, IMRT technique and type of fractionation were not found to be prognostic factor on local control. Nine patients experienced Grade 3-4 acute laryngeal edema (Gr 3; 8 patients, Gr 4; 1 patient), and 3 patients experienced grade 3-4 late laryngeal edema (Gr 3; 2 patients, Gr 4; 1 patients). The second primary cancer was seen in 18 (9%) cases. No transient ischemic attack or stroke was observed. Oncologic outcomes of patients treated with carotid sparing IMRT were excellent with acceptable side effect. Long-term follow-up is needed to demonstrate outcomes for long-term toxicity.

Do Higher Radiation Doses with Concurrent Chemotherapy in the Definitive Treatment of Esophageal Cancer Improve Outcomes? A Meta-Analysis and Systematic Review

For non-operable, localized esophageal carcinoma (EC), definitive concurrent chemoradiotherapy (dCCRT) is usually the standard treatment approach. Currently, the dCCRT radiation dose recommended by National Comprehensive Cancer Network (NCCN) is 50.4 Gy, which is primarily based on results of the Radiation Therapy Oncology Group (RTOG)85-01 and 94-05 randomized trials. However, the optimal radiation dose in this scenario remains controversial. Radiation dose escalation has been proposed as a technique to obtain higher local-regional control (LRC) and survival rates, notably in Asian countries. Additionally, with advances in radiotherapy techniques, questions have been raised as to whether dose escalation utilizing computerized tomography (CT)-based radiotherapy approaches (including 3-D, IMRT and proton therapy) could achieve improved outcomes with less toxicity compared to older approaches from the 2-D era. The aim of the study is to investigate the effects and safety profile of radiation dose escalation utilizing computerized tomography (CT) based modern techniques (including 3-D, IMRT, SIB-IMRT and proton therapy) in the definitive treatment of patients with EC with dCCRT. Studies published prior to 15 February, 2020 comparing radiation dose and disease-related outcomes in nonoperable EC patients were included. All relevant studies utilizing CT-based radiation planning, comparing high-dose (≥ 60 Gy) versus standard-dose (50.4 Gy) radiation for patients with EC were analyzed for this meta-analysis. Eleven studies including 4946 patients met the inclusion criteria, including 4775 (96.5%) ESCC patients, 142 EAC patients and 30 patients with other histology. The high-dose group demonstrated a significant improvement in local-regional failure (LRF) (OR 2.199, 95% CI 1.487-3.253; P<0.001), two-year local-regional control (LRC) (OR 0.478, 95% CI 0.309-0.740; P = 0.001), two-year overall survival (OS) (HR 0.744, 95% CI 0.657-0.843; P<0.001) and five-year OS (HR 0.683, 95% CI 0.561-0.831; P<0.001) rates relative to the standard-dose group. In addition, there was no difference in grade≥ 3 acute radiation-related toxicities and treatment-related deaths between the groups. The study demonstrated that compared to the standard radiation-doses, dose-escalated (≥60Gy), CT-based radiotherapy techniques may improve ultimate survival in patients with inoperable ESCC under the premise of controlling the rate of toxicities, and represents the first meta-analysis comparing high versus standard radiation doses utilizing CT-based/modern radiotherapy techniques. Our results support this approach as well as the multiple ongoing randomized trials further evaluating this strategy.

Correlation of clinical outcome, radiobiological modeling of tumor control, normal tissue complication probability in lung cancer patients treated with SBRT using Monte Carlo calculation algorithm.

Purpose/BackgroundWe analyzed the predictive value of non‐x‐ray voxel Monte Carlo (XVMC)‐based modeling of tumor control probability (TCP) and normal tissue complication probability (NTCP) in patients treated with stereotactic body radiotherapy (SBRT) using the XVMC dose calculation algorithm.Materials/MethodsWe conducted an IRB‐approved retrospective analysis in patients with lung tumors treated with XVMC‐based lung SBRT. For TCP, we utilized tumor size‐adjusted biological effective dose (s‐BED) TCP modeling validated in non‐MC dose calculated SBRT to: (1) verify modeling as a function of s‐BED in patients treated with XVMC‐based SBRT; and (2) evaluate the predictive potential of different PTV dosimetric parameters (mean dose, minimum dose, max dose, prescription dose, D95, D98, and D99) for incorporation into the TCP model. Correlation between observed local control and TCPs was assessed by Pearson's correlation coefficient. For NTCP, Lyman NTCP Model was utilized to predict grade 2 pneumonitis and rib fracture.ResultsEighty‐four patients with 109 lung tumors were treated with XVMC‐based SBRT to total doses of 40 to 60 Gy in 3 to 5 fractions. Median follow‐up was 17 months. The 2‐year local and local‐regional control rates were 91% and and 78%, respectievly. All estimated TCPs correlated significantly with 2‐year actuarial local control rates (P < 0.05). Significant corelations between TCPs and tumor control rate according to PTV dosimetric parameters were observed. D99 parameterization demonstrated the most robust correlation between observed and predicted tumor control. The incidences of grade 2 pneumonitis and rib fracture vs. predicted were 1% vs. 3% and 10% vs. 13%, respectively.ConclusionOur TCP results using a XVMC‐based dose calculation algorithm are encouraging and yield validation to previously described TCP models using non‐XVMC dose methods. Furthermore, D99 as potential predictive parameter in the TCP model demonstrated better correlation with clinical outcome.

The Utility of Diffusion and Perfusion Magnetic Resonance Imaging in Target Delineation of High-Grade Gliomas.

Background The tumor volume of high-grade glioma (HGG) after surgery is usually determined by contrast-enhanced MRI (CE-MRI), but the clinical target volume remains controversial. Functional magnetic resonance imaging (multimodality MRI) techniques such as magnetic resonance perfusion-weighted imaging (PWI) and diffusion-tensor imaging (DTI) can make up for CE-MRI. This study explored the survival outcomes and failure patterns of patients with HGG by comparing the combination of multimodality MRI and CE-MRI imaging with CE-MRI alone. Methods 102 patients with postoperative HGG between 2012 and 2016 were included. 50 were delineated based on multimodality MRI (PWI, DTI) and CE-MRI (enhanced T1), and the other 52 were delineated based on CE-MRI as control. Results The median survival benefit was 6 months. The 2-year overall survival, progression-free survival, and local–regional control rates were 48% vs. 25%, 42% vs. 13.46%, and 40% vs. 13.46% for the multimodality MRI and CE-MRI cohorts, respectively. The two cohorts had similar rates of disease progression and recurrence but different proportions of failure patterns. The univariate analysis shows that characteristics of patients such as combined with epilepsy, the dose of radiotherapy, the selection of MRI were significant influence factors for 2-year overall survival. However, in multivariate analyses, only the selection of MRI was an independent significant predictor of overall survival. Conclusions This study was the first to explore the clinical value of multimodality MRI in the delineation of radiotherapy target volume for HGG. The conclusions of the study have positive reference significance to the combination of multimodality MRI and CE-MRI in guiding the delineation of the radiotherapy target area for HGG patients.

The Efficacy of Low Postoperative Radiation Dose in Patients with Advanced Hypopharyngeal Cancer without High-Risk Factors.

ObjectiveTo evaluate the feasibility and efficacy of low postoperative radiotherapy (PORT) dose in patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC) and identify prognostic factors in this group.Patients and MethodsBetween January 2013 and September 2015, 110 consecutive patients with HPSCC with no high-risk factors were treated postoperatively to 50 Gy (n=89), 56 Gy (n=12), and 60 Gy (n=9) in 2 Gy/fraction. Overall survival (OS), 3-year progression-free survival (PFS), 3-year loco-regional recurrence-free survival (LRFS), and treatment-related toxicities were analyzed.ResultsMedian follow-up time was 40 months (range=6–75 months). The 3-year local-regional control (LRC) and 3-year neck control rate were 86.3% and 91.8%, respectively. The 3-year OS, PFS, and LRFS were 69.9%, 65.5%, and 80.5%, respectively. In a univariate analysis, T stage showed a significant correlation with improved OS, PFS, and LRFS (P=0.008, P=0.039, P=0.034). On multivariate analysis, T stage showed a significant correlation with improved OS and PFS. N stage showed a significant correlation with improved PFS. However, interval surgery-radiotherapy, reconstructive methods, and RT dose cannot serve as a significant prognostic factor for survival outcome.ConclusionThis study suggests that treating no high-risk factors for locally advanced HPSCC with a dose of 50 Gy to the whole operative bed and elective lymph node levels cannot compromise disease control and survival.

Locoregional control, failure patterns and clinical outcomes in patients with stage III non-small cell lung cancers treated with chemoradiation and durvalumab.

e21058 Background: Definitive concurrent chemoradiation (cCRT) and durvalumab is a standard therapy for patients with unresectable stage III non-small cell lung cancers (NSCLC). Data is limited on outcomes with this regimen outside of clinical trials. Local-regional control rates to date remain undefined. Methods: We reviewed patients with stage III unresectable NSCLC treated between November 2017 and February 2019 with cCRT. Patients that received at least one cycle of durvalumab were further assessed for 12-month progression free survival (PFS), overall survival (OS), and the incidence and pattern of local-regional and metastatic failures. Disease-relapse was characterized to determine patients potentially eligible for metastasis-directed ablative therapies. Toxicities leading to durvalumab discontinuation were evaluated using CTCAE v.5.0. Results: Of the 83 patients with stage III NSCLC treated with cCRT (median 60Gy), 62 received durvalumab and were evaluable (median follow-up: 12 months). Patients (n = 21, 25%) did not receive durvalumab largely related to metastatic progression (n = 9) or persistent cCRT toxicity (n = 10). In the 62 durvalumab treated patients the median age was 66 (range: 49 - 86), 73% had stage IIIB (n = 33) or IIIC (n = 12) disease, and 58% (n = 36) had adenocarcinoma. The median time from cCRT end to durvalumab start was 1.5 months. Patients received a median of 8 months of durvalumab; 35% (n = 22) of patients completed 12 months of therapy. Common reasons for discontinuing durvalumab included disease progression (32%, 20/62) and toxicity (24%, 15/62). The estimated 12-month PFS and OS were 65% (95% CI: 51 - 79%) and 85% (95% CI: 75 - 95%), respectively. High TMB (≥ 8.8 mt/Mb) or PD-L1 (≥ 1% or PD-L1 ≥ 50%) did not predict improved PFS. Patients who discontinued durvalumab due to toxicity did not have inferior PFS. The cumulative 12-month incidence of local-regional and distant metastatic failures were 18% (95% CI: 5.9 - 30%) and 30% (95% CI: 16.3 - 44.5%), respectively. Of the 17 patients with distant metastases, 9 had oligometastases and would have been potential candidates for comprehensive ablative therapies. Conclusions: Outcomes and toxicities outcomes with cCRT and durvalumab in clinical practice align with the PACIFIC trial. Analysis of disease-relapse suggests a substantial minority of patients with disease progression may be potential candidates for metastasis-directed therapies. Local regional outcomes appear improved to historical data of cCRT alone.

Outcomes and toxicity after salvage radiotherapy for vaginal relapse of endometrial cancer

ObjectivesStudies of salvage radiotherapy in locally recurrent endometrial cancer remain limited. The aim of this study was to evaluate the efficacy of salvage radiotherapy for vaginal relapse of endometrial cancer...

Clinical outcomes, local–regional control and the role for metastasis-directed therapies in stage III non-small cell lung cancers treated with chemoradiation and durvalumab

Background and purposeConcurrent chemoradiation (cCRT) and durvalumab is standard therapy for patients with unresectable stage III non-small-cell lung cancers (NSCLC). Data is limited on outcomes with this regimen outside of clinical trials. Local-regional control rates remain undefined. Materials and methodsWe reviewed patients with stage III unresectable NSCLCs treated between November 2017 and February 2019 with cCRT and ≥1 dose of durvalumab. We examined 12-month progression-free-survival (PFS), overall-survival (OS), toxicities, and the incidence and pattern of local–regional and metastatic failures. ResultsSixty-two patients (median follow-up 12 months) with median age of 66 years of which 73% had stage IIIB (n = 33) or IIIC (n = 12) disease started durvalumab a median of 1.5 months from the end of cCRT and were treated with a median of 8 months of durvalumab. Common reasons for stopping durvalumab included disease progression (32%, 20/62) and toxicity (24%, 15/62). The estimated 12-month PFS and OS were 65% (95% CI: 51–79%) and 85% (95% CI: 75–95%), respectively. The cumulative 12-month incidence of local–regional and distant failures were 18% (95% CI: 5.9–30%) and 30% (95% CI: 16.3–44.5%), respectively. Among patients with distant metastatic disease (n = 17), 47% had oligometastatic disease. High tumor mutation burden (≥8.8 mt/Mb) or PD-L1 (≥1% or PD-L1 ≥ 50%) did not predict improved PFS. ConclusionsOutcomes with cCRT and durvalumab in practice align with the PACIFIC trial. A substantial minority of patients are candidates for metastasis-directed therapies at progression. Local regional outcomes appear improved to historical data of cCRT alone.

Outcomes and toxicities following stereotactic ablative radiotherapy for pulmonary metastases in patients with primary head and neck cancer.

Metastatic head and neck cancers (HNCs) predominantly affect the lungs and have a two-year overall survival (OS) of 15% to 50%, if amenable for pulmonary metastasectomy. Retrospective review of the two-year local control (LC), local-regional control (LRC) within the same lobe, OS, and toxicity rates in consecutive patients with metastatic pulmonary HNC who underwent stereotactic ablative radiotherapy (SABR) January 2007 to May 2018. Evaluated 82 patients with 107 lung lesions, most commonly squamous cell carcinoma (SCC; 64%). Median follow-up was 20 months (range: 9.0-97.6). Systemic therapy administered in 34%. LC, LRC, and OS rates were 94%, 90%, and 62%. Patients with oligometastatic disease had a higher OS than polymetastatic disease, 72% vs 44% (HR = 0.30, 95% CI: 0.14-0.64; P = .008). OS in oligometastatic non-SCC and SCC were 100% and 66% (P = .03). There were no grade ≥3 toxicities. Metastatic pulmonary HNCs after SABR have a two-year OS rate comparable to pulmonary metastasectomy.

Patterns of Failure in Parameningeal Alveolar Rhabdomyosarcoma

To determine patterns of failure, clinical outcomes, and prognostic factors among pediatric patients treated with radiation therapy for parameningeal alveolar rhabdomyosarcoma. We evaluated clinical and treatment planning records of patients aged ≤21 years with parameningeal alveolar rhabdomyosarcoma treated with definitive or adjuvant radiation therapy at our institution. The Kaplan-Meier product limit method assessed disease control and survival; the log-rank test was used to evaluate prognostic impact. We identified 24 patients with a median age of 3.5 years (range, 1-20) treated between 2009 and 2016. The median follow-up was 2.4 years for all (range, 0.3-5.6) and 3.2 years for living patients (range, 0.7-5.6). Most patients had group III (96%), node-negative (67%), positive FOX fusion status (63%) disease, and intracranial extension (54%). The paranasal sinus was the most common subsite (29%). All patients were treated with concurrent chemotherapy and proton radiation therapy with a median dose of 50.4 Gy relative biological effectiveness (range, 41.4-59.4) at a median 13 weeks after induction chemotherapy (range, 3-25). The 3-year local control, regional control, disease-free survival, and overall survival rates were 66%, 94%, 40%, and 58%, respectively. Median time to any failure was 0.5 years (range, 0.2-2.1). N1 disease and intracranial extension (ICE) portended inferior overall survival (P = .002 and .02, respectively). Female sex portended better local control (P= .05). All 7 patients with distant metastases as the first site of recurrence had central nervous system metastases. Age <4 years, absence of ICE, N0 disease, and primary tumor <5 cm were associated with a statistically significant improvement in freedom from distant metastases. Although regional nodal failures were rare, in-field local recurrences and leptomeiningeal progression in those with ICE suggest the need for modification of local and central nervous system therapies.

Clinical Outcomes of Patients With Unresectable Cholangiocarcinoma Treated With Proton Beam Therapy.

To investigate the clinical outcomes and failure patterns of patients with unresectable cholangiocarcinoma (CC) who had been treated with proton beam therapy (PBT). The authors retrospectively examined 30 patients with unresectable CC who had undergone PBT between November 2015 and December 2017. Survival curves were plotted with the Kaplan-Meier method. Independent predictors of survival were identified by multivariate Cox proportional hazard regression analyses. Complications were assessed using the Common Terminology Criteria for Adverse Events v4.0. The median tumor size was 7 cm. Seventeen patients (56.7%) had regional lymph node metastases. The median radiation dose was 72.6 cobalt gray equivalents, and 23 patients (76.7%) received concurrent chemotherapy. The 1-year local control, regional control, and distant metastases-free rates were 88%, 86%, and 68%, respectively. The median overall survival and progression-free survival were 19.3 and 10.4 months, respectively. The median jaundice-free survival was 13 months, with a 1-year biliary tract infection (BTI)-free rate of 58%. Patients who received concurrent chemotherapy had a better median progression-free survival (12.1 vs. 4.7 mo). The most common form of acute toxicity from PBT was acute skin reactions which were rarely severe (grade III: 7% of patients). Three and 2 patients had grade III-IV toxicities and radiation-induced liver disease. There were no deaths caused by PBT or concurrent chemotherapy. PBT is clinically useful in patients with unresectable CC, even in the presence of large tumors or regional nodal metastases. Its use may induce durable symptom relief, without increasing acute or late toxicity.

Postoperative radiotherapy in resected sinonasal mucosal melanoma.

e21059 Background: Mucosal melanoma is rare but highly aggressive. Sinonasal melanoma comprised approximately 26% of the whole mucosal melanoma. Complete surgery plus postoperative radiotherapy is often recommended for early-stage sinonasal melanoma patients. However, the role of postoperative radiotherapy is still disputable. Methods: Mucosal melanoma patients with stage I-III sinonasal primaries which were completely resected were enrolled as part of the multicenter, randomized, controlled, phase 3 trial for the comparison of adjuvant chemotherapy (TMZ plus DDP 6 cycles) with high-dose interferon (HDI, 1 year) (NCT03435302). Postoperative radiotherapy was recommended in the trial for their own choice, prescribed as GTV 60-70Gy/CTV 60Gy/30f. Patients were divided into two groups, those who completed adjuvant radiotherapy after surgery (group S+R, n = 41) and those who received surgery alone (group S, n = 32). Results: Seventy three patients were enrolled from Feb 2014 to Jun 2016. Two groups were balanced regarding to age, gender, and adjuvant therapy of either HDI or chemotherapy. There are more locally advanced patients in Group S, namely T3-4 or N positive ( P= 0.001). At a median follow-up of 31.2 months (range: 5.3-60.0m), the median RFS was not reached in the S+R group, as compared with 17.1 months (95% CI: 2.3-31.9m, P= 0.008) in the S group. The median DMFS was 27.2 months (95% CI: 19.3-35.1m) in the S+R group, as compared with 24.8 months (95% CI: 13.9-35.7m, P= 0.475) in the S group. Patients in the S group had an increased probability of locoregional recurrence as a first event (46.7% vs. 14.6%), while patients in the S+R group are more likely to have metastases first (41.5% vs. 12.5%). Estimated OS was 46.8 months in the S+R group and 37.3 months (95% CI: 20.8-53.8m, P= 0.097) in the S group. T&amp;N staging also had an influence on RFS, DMFS, and OS. In COX multivariate analysis, T&amp;N staging was the only significant prognostic factor. Common toxicities included mucositis, dermatitis, nausea, and leukopenia. Conclusions: This study suggested that postoperative radiotherapy improved local-regional control rate and might had no effect on DMFS. OS was better in radiotherapy group but still mostly depends on T&amp;N staging. More prospective data are needed for this subtype of melanoma. Clinical trial information: NCT03435302.

Outcomes after Definitive Re-Irradiation with 3D Brachytherapy with or without External Beam Radiation Therapy for Vaginal Recurrence of Endometrial Cancer

Abstract Background Limited outcome data exists on salvage re-irradiation for vaginal relapse of previously-irradiated endometrial cancer. We report our 10-year experience with management of vaginal recurrence using definitive intent re-irradiation brachytherapy with or without EBRT. Methods A retrospective review was performed on 22 patients treated with definitive-intent re-irradiation brachytherapy ± EBRT for vaginal recurrence of endometrial cancer. The cumulative rectosigmoid and bladder D2cc (EQD2) were limited to Results Prior radiation therapy consisted of vaginal brachytherapy (54.5%), pelvic EBRT (22.7%), or combination pelvic EBRT and brachytherapy (22.7%). Median re-irradiation interval was 26.6 months. Salvage re-irradiation consisted of EBRT with brachytherapy in 50.0% and brachytherapy alone in 50.0%. Median HR-CTV D90 (EQD2) was 64.5 Gy (IQR: 49.6–75.8). Median cumulative D2cc for bladder, rectum, and sigmoid were 72.1 Gy (range: 30.3–81.8), 70.6 Gy (range: 32.0–80.5), and 52.7 Gy (range: 29.6–75.3), respectively. At a median follow-up of 27.6 months, 3-year local control, regional control, disease-free survival, and overall survival rates were 65.8%, 76.6%, 40.8%, and 68.1%, respectively. There were no grade ≥ 3 acute or late rectosigmoid or bladder toxicities. Conclusion Re-irradiation with 3D conformal brachytherapy for vaginal recurrence is feasible and safe as long as cumulative dose to surrounding normal organs is limited, and offers a chance to potentially salvage 40% of patients presenting with vaginal recurrence in the setting of prior pelvic radiation.

Nutritional and clinical outcomes of chemoradiotherapy for clinical T1N0M0 esophageal carcinoma.

Purpose: Whether nutritional assessment and management improves clinical outcomes in patients with clinical T1N0M0 esophageal squamous cell carcinoma (ESCC) who undergo chemoradiotherapy remains to be demonstrated. This study aimed to determine the nutritional status of such patients pre- and post-chemoradiotherapy and its clinical outcomes.Patients and methods: This single institutional retrospective study included patients who underwent chemoradiotherapy for clinical T1N0M0 ESCC using serum albumin concentrations and body weights evaluated pre- and post-chemoradiotherapy from January 2005 to December 2016. The nutritional risk index (NRI) score was used to quantify the nutritional status: NRI score ≥100: no risk, 97.5–100: mild risk, 83.5–97.5: moderate risk, and <83.5: major risk. NRI categories pre-and post-chemoradiotherapy were compared using Wilcoxon signed rank test. Local-regional control (LRC), overall survival (OS), and cause-specific survival (CSS) rates were calculated using Kaplan–Meier method. The effect of pre-chemoradiotherapy NRI score and decreased NRI category during chemoradiotherapy on OS was evaluated using log-rank test.Results: Among the 492 patients with ESCC who underwent chemoradiotherapy, 44 were included in this study. Among these, 21 patients exhibited a pre-chemoradiotherapy NRI score of <100. During chemoradiotherapy, the NRI score decreased from 100.5 to 94.5, and the median NRI category significantly decreased by 2 (p<0.0001). With a median follow-up of 72 months, the 5-year LRC, OS, and CSS rates were 79.8%, 88.9%, and 96.8%, respectively. The pre-chemoradiotherapy NRI score of <100 and decreased NRI category during chemoradiotherapy did not significantly affect OS.Conclusion: Patients with clinical T1N0M0 ESCC without dysphagia were at risk of undernutrition pre- and post-chemoradiotherapy. The current study’s results justify further clinical nutritional research for this population, and that clinicians consider nutritional support for this population.

Outcomes after definitive re-irradiation with 3D brachytherapy with or without external beam radiation therapy for vaginal recurrence of endometrial cancer

BackgroundLimited outcome data exists on salvage re-irradiation for vaginal relapse of previously-irradiated endometrial cancer. We report our 10-year experience with management of vaginal recurrence using definitive intent re-irradiation brachytherapy with or without EBRT. MethodsA retrospective review was performed on 22 patients treated with definitive-intent re-irradiation brachytherapy ± EBRT for vaginal recurrence of endometrial cancer. The cumulative rectosigmoid and bladder D2cc (EQD2) were limited to <75 Gy and <90 Gy, respectively. Kaplan-Meier and Cox proportional hazards modeling were used to estimate survival. Severe (grade 3 or higher) radiation-related toxicities, defined according to CTCAE v4, were recorded. ResultsPrior radiation therapy consisted of vaginal brachytherapy (54.5%), pelvic EBRT (22.7%), or combination pelvic EBRT and brachytherapy (22.7%). Median re-irradiation interval was 26.6 months. Salvage re-irradiation consisted of EBRT with brachytherapy in 50.0% and brachytherapy alone in 50.0%. Median HR-CTV D90 (EQD2) was 64.5 Gy (IQR: 49.6–75.8). Median cumulative D2cc for bladder, rectum, and sigmoid were 72.1 Gy (range: 30.3–81.8), 70.6 Gy (range: 32.0–80.5), and 52.7 Gy (range: 29.6–75.3), respectively. At a median follow-up of 27.6 months, 3-year local control, regional control, disease-free survival, and overall survival rates were 65.8%, 76.6%, 40.8%, and 68.1%, respectively. There were no grade ≥ 3 acute or late rectosigmoid or bladder toxicities. ConclusionRe-irradiation with 3D conformal brachytherapy for vaginal recurrence is feasible and safe as long as cumulative dose to surrounding normal organs is limited, and offers a chance to potentially salvage 40% of patients presenting with vaginal recurrence in the setting of prior pelvic radiation.

Intensity-modulated radiotherapy combined with sequential cisplatin and fluorouracil chemotherapy for locoregionally advanced nasopharyngeal carcinoma.

To investigate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) combined with induction-adjuvant cisplatin and fluorouracil (PF) in locoregionally advanced nasopharyngeal carcinoma (NPC).A total of 91 biopsy-proven NPC patients treated with IMRT were retrospectively analyzed. All patients received induction chemotherapy (IC) consisting of cisplatin 25 mg/m2 on day 1 to 3, and 5-Fu 2500 mg/m2 as an intravenous infusion over 120 hours every 3 weeks for 2 cycles. Adjuvant chemotherapy of the same regime was given 28 days after the end of IMRT.A total of 87 patients completed 2 cycles of IC. During adjuvant chemotherapy phase, 74.7% patients received at least 1 cycle. With a median follow-up time of 45 months (10–123 months), the 5-year local control, regional control, distant metastasis-free (DMF) and overall survival (OS) rates were 84.1%, 86.9%, 81.3%, and 74.4%, respectively. The 5-year local control rates for patients with Stage T1-2 and T3-4 was 94.6% and 76.5%, respectively (P = .045). The 5-year DMF rates for patients with N0-1 and N2-3 diseases were 90.6% and 73.3%, respectively (P = .072). During radiotherapy (RT), 24.2% patients suffered severe acute mucositis (grade 3–4). Severe late toxicities included cranial nerve palsy in 1 patient and grade 3 hearing impairment in 1 patient.IMRT combined with induction-adjuvant chemotherapy consisting of PF regimen is well tolerated and provides satisfactory local-regional control for locoregionally advanced NPC. Further treatment strategies to control distant metastasis are needed in the future.

Image-based Multichannel Vaginal Cylinder Brachytherapy for the Definitive Treatment of Vaginal Cancers

Brachytherapy (BT) is integral to vaginal cancer treatment and is typically delivered using either an intracavitary single-channel vaginal cylinder or an interstitial BT (ISBT) applicator. Multi-channel vaginal cylinder (MCVC) applicators allow for improved organ-at-risk (OAR) sparing compared to single-channel applicators while maintaining target coverage and avoiding ISBT implantations in selected patients (pts). We present clinical outcomes of pts treated with image-based high-dose-rate (HDR) BT using a MCVC. Sixty pts with vaginal cancer (27% primary vaginal and 73% recurrence from gynecologic primaries) were treated with combination external beam radiotherapy (EBRT) and image-based HDR BT utilizing MCVC from 2011 to 2016. Pts were selected for treatment with MCVC only if residual disease thickness was ≤7 mm after EBRT. The BT high-risk clinical target volume (CTVHR) included the circumferential vaginal surface as defined by the length of the pre-EBRT gross tumor volume (GTV) from both imaging and clinical examination, and the post-EBRT GTV defined the area for which the entire thickness of the vagina and residual tumor would be included. Total EBRT and BT doses were summated and converted to equivalent dose in 2 Gy fractions (EQD2 Gy). All pts received 3D image-based BT to a total equivalent dose of 70-80 Gy. Nineteen pts (32%) received concurrent chemotherapy with EBRT, and 7 (12%) received adjuvant systemic therapy. After a median follow-up of 45 months (range, 11-78), complete clinical response was documented in 98% of pts. The median CTVHR volume was 24.4 cc (interquartile range [IQR], 14.1), with a median dose delivered to 90% of CTVHR of 77.2 EQD2 Gy (IQR, 2.8). The 4-year local-regional control (LRC), distant control, disease-free survival, and overall survival rates were 92.6%, 76.1%, 64.0%, and 67.2%, respectively. There were no significant differences in LRC by any of the examined patient and treatment factors. The 4-year LRC rates were similar between the primary vaginal (92%) and recurrent (93%) groups (p=0.290). Pts with lymph node positive disease had a lower rate of distant control at 4 years (22.7% vs. 89.0%, p<0.001). There were no Grade 3 or higher acute complications. The 4-year rate of late Grade 3 or higher toxicity was 2.7%. One patient developed a severe small bowel toxicity manifested as adhesions of the terminal ileum 13 months after treatment. Clinical outcomes of pts with primary and recurrent vaginal cancer treated definitively in a systematic manner with combination EBRT with image-guided HDR BT utilizing a MCVC applicator demonstrate high rates of local control and low rates of severe morbidity. The MCVC technique allows interstitial implantation to be avoided in select pts with ≥7 mm residual disease thickness following EBRT while maintaining excellent clinical outcomes with extended 4-year follow-up in this rare malignancy.