scholarly journals Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer

2020 ◽  
Vol 38 (14) ◽  
pp. 1569-1579 ◽  
Author(s):  
Steven H. Lin ◽  
Brian P. Hobbs ◽  
Vivek Verma ◽  
Rebecca S. Tidwell ◽  
Grace L. Smith ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Radiation Therapy ◽  
Interim Analysis ◽  
Locally Advanced ◽  
Intensity Modulated Radiation Therapy ◽  
Proton Beam Therapy ◽  
Advanced Esophageal Cancer ◽  
Intensity Modulated ◽  
Locally Advanced Esophageal Cancer

PURPOSE Whether dosimetric advantages of proton beam therapy (PBT) translate to improved clinical outcomes compared with intensity-modulated radiation therapy (IMRT) remains unclear. This randomized trial compared total toxicity burden (TTB) and progression-free survival (PFS) between these modalities for esophageal cancer. METHODS This phase IIB trial randomly assigned patients to PBT or IMRT (50.4 Gy), stratified for histology, resectability, induction chemotherapy, and stage. The prespecified coprimary end points were TTB and PFS. TTB, a composite score of 11 distinct adverse events (AEs), including common toxicities as well as postoperative complications (POCs) in operated patients, quantified the extent of AE severity experienced over the duration of 1 year following treatment. The trial was conducted using Bayesian group sequential design with three planned interim analyses at 33%, 50%, and 67% of expected accrual (adjusted for follow-up). RESULTS This trial (commenced April 2012) was approved for closure and analysis upon activation of NRG-GI006 in March 2019, which occurred immediately prior to the planned 67% interim analysis. Altogether, 145 patients were randomly assigned (72 IMRT, 73 PBT), and 107 patients (61 IMRT, 46 PBT) were evaluable. Median follow-up was 44.1 months. Fifty-one patients (30 IMRT, 21 PBT) underwent esophagectomy; 80% of PBT was passive scattering. The posterior mean TTB was 2.3 times higher for IMRT (39.9; 95% highest posterior density interval, 26.2-54.9) than PBT (17.4; 10.5-25.0). The mean POC score was 7.6 times higher for IMRT (19.1; 7.3-32.3) versus PBT (2.5; 0.3-5.2). The posterior probability that mean TTB was lower for PBT compared with IMRT was 0.9989, which exceeded the trial’s stopping boundary of 0.9942 at the 67% interim analysis. The 3-year PFS rate (50.8% v 51.2%) and 3-year overall survival rates (44.5% v 44.5%) were similar. CONCLUSION For locally advanced esophageal cancer, PBT reduced the risk and severity of AEs compared with IMRT while maintaining similar PFS.

Interim analysis of a phase II study of simultaneously integrated boost intensity modulated radiation therapy (SIB-IMRT) in combination with 5-FU and mitomycin-C among patients with locally advanced anal canal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15501-e15501
Author(s):  
Carmen Florescu ◽  
Justine Lequesne ◽  
Jean-Michel Grellard ◽  
Aurélie Parzy ◽  
Marie-Pierre Galais ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Anal Canal ◽  
Mitomycin C ◽  
Interim Analysis ◽  
Locally Advanced ◽  
Intensity Modulated Radiation Therapy ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Intensity Modulated ◽  
Phase 2 Trial

e15501 Background: Concomitant radiochemotherapy is the standard treatment of locally advanced epidermoid anal canal carcinoma (EACC) but conventional radiotherapy (RT) frequently induces significant non-hematological toxicities, resulting in long treatment breaks. Given the numerous anatomic pelvic structures, EACC has become of interest for Intensity-Modulated Radiation Therapy (IMRT) despite the induced cutaneous toxicities responsible for RT breaks. Given the deleterious effect of treatment duration on local control and survival in other epidermoid cancers, continuous IMRT is challenging to control EACC. Several SIB-IMRT schedules provided similar results with moderate doses and schedules delivering higher doses with short breaks. Yet, standard SIB-IMRT schedule in EACC still not exists. We propose to concomitantly assess the safety and efficacy of continuous SIB-IMRT without planned breaks and concurrent chemotherapy (CT) to improve the treatment of locally advanced EACC by reducing the proportion of patients (pts) requiring RT breaks for toxicities. Methods: The CANAL-IMRT-01 phase 2 trial (NCT02701088) targets pts with histologically proven EACC candidate for concomitant RT of pelvic and inguinal nodes plus CT. Applying a two-step Bryant & Day design, the main criterion is based on both efficacy and safety. Efficacy is defined as the proportion of pts alive with no local disease progression 3 months after the end of IMRT; safety is defined as the proportion of pts with no RT breaks required by grade ≥3 toxicities. Assuming the unacceptable and acceptable proportions of pts without toxicity requiring IMRT break are 60 and 80% respectively, the unacceptable and acceptable 3-month-progression-free-survival are 80 and 90%, 14 assessable pts at first step and 46 in the second are required (alpha risk 5%, 90% power). To anticipate a 10% drop out rate, 16 pts were needed in first step, with ≥11 objective local responses and ≤6 toxicity-induced IMRT breaks to pursue. Treatment consists in 50 days of concomitant CT (2 cycles of 5FU and Mitomycin-C) and SIB-IMRT delivered by helical tomotherapy: 61.2Gy/1.7Gy to the primary tumor, 57.6Gy/1.6Gy to involved nodes, and 54/1.5Gy to elective pelvic lymph nodes. Results: From December 2015 to June 2017, 16 pts were enrolled: 11 female (73%), median age 62 [55-66]. 15 pts were assessable for efficacy and safety. All 15 pts had a 3-month locoregional response (12 complete responses, 3 partial responses). SIB-IMRT breaks were required by toxicities for 4 out of 15 pts: G1 radiodermitis, G2 inguinal and epithelitis, G1 fever, G3 anorexia and vertigo. Conclusions: The planned interim analysis of continuous SIB-IMRT plus CT allowed pursuing this phase 2 trial to assess the relevance of such schedule for locally advanced ASCC. Enrolment is still ongoing. Clinical trial information: NCT02701088.

Phase II cisplatin, irinotecan, cetuximab and concurrent radiation therapy followed by surgery for locally advanced esophageal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4064-4064 ◽  
Author(s):  
P. C. Enzinger ◽  
T. Yock ◽  
W. Suh ◽  
P. Fidias ◽  
H. Mamon ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Radiation Therapy ◽  
Phase Ii ◽  
Locally Advanced ◽  
Complete Response ◽  
Tumor Location ◽  
Advanced Esophageal Cancer ◽  
Early Results ◽  
Ecog Ps ◽  
Locally Advanced Esophageal Cancer

4064 Background: Weekly irinotecan, cisplatin, and concurrent radiation therapy is a well-tolerated, active regimen in locally advanced esophageal cancer. (Ilson. JCO 2003) Cetuximab, an EGFR inhibitor, is a potent radiation sensitizer in head and neck cancer. (Bonner. Proc ASCO 2004) Methods: In this phase II trial, patients (pts) with T2–4N0–1M0–1A esophageal adenocarcinoma (A) or squamous cell carcinoma (S) receive 5040 cGy/28 fractions of radiation therapy (RT) and concurrent weekly cisplatin 30mg/m2 plus irinotecan 65 mg/m2 on weeks 1, 2, 4, and 5, followed by surgery 4–8 weeks after completion of RT. Additionally, pts receive weekly infusions of cetuximab 250 mg during RT, up to one week before surgery, and for 6 months following surgery. Results: Seventeen pts have been entered: male: female = 14:3, median age 54, ECOG PS 0:1 = 6:11, A:S = 17:0, stage IIA:IIB:III:IVA = 6:1:8:2, tumor location-esophagus-mid:lower:gastroesophageal junction = 1:4:12, >10% weight loss-yes:no = 8:9. Of 17 pts entered, 15 pts have proceeded to surgery, 1 pt died from Aspergillus infection resulting in respiratory failure and sepsis, and 1 pt is pending surgery. Of the 15 pts who underwent surgery, 2 (13%) had a complete pathologic response; pathologic stage for other pts: 0 = 1, I = 3, IIA = 3, IIB = 1, III = 4, IV = 1. Grade III/IV toxicity (17 pts) was: diarrhea 9 pts, neutropenia 9 pts, febrile neutropenia 5 pts, anorexia 5 pts, vomiting 4 pts, fatigue 3 pts, mucositis 1 pt. Chemotherapy dose attenuation was required for diarrhea in 5 pts, for neutropenia in 4 pts, and for folliculitis in 1 pt. One patient was removed from study during week 6 for prolonged diarrhea/ dehydration. Due to the 2-step design of the trial, accrual is on hold pending a 3rd required pathologic CR in the first 17 patients. Conclusions: Compared to other trials of irinotecan, cisplatin, radiation therapy, and surgery in similar groups of esophageal cancer patients, early results for this combination with cetuximab suggest a lower complete response rate and higher overall toxicity. Additional data will be available at ASCO. Supported by Bristol-Myers Squibb. No significant financial relationships to disclose.

Patterns of failure following tri-modality therapy for locally advanced esophageal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 203-203
Author(s):  
Talha Shaikh ◽  
Mark A. Zaki ◽  
Michael M. Dominello ◽  
Elizabeth Handorf ◽  
Andre A. Konski ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Lymph Nodes ◽  
Metastatic Disease ◽  
Locally Advanced ◽  
Post Treatment ◽  
Advanced Esophageal Cancer ◽  
Patterns Of Failure ◽  
Cancer Data ◽  
Locally Advanced Esophageal Cancer

203 Background: Although tri-modality therapy is an acceptable standard of care in patients with locally advanced esophageal cancer, data regarding patterns of failure is lacking. We report bi-institutional patterns of failure experience treating patients using tri-modality therapy. Methods: Following IRB approval, we retrospectively reviewed all pts who underwent chemoradiation followed by esophagectomy at two NCI-designated cancer centers from 2000-2013. Patient and treatment factors were analyzed for failure patterns. First failure sites were categorized as local, regional nodal, or distant. Statistical analysis was performed using Fisher’s exact test and non-parametric Wilcoxon rank-sum test. Results: A total of 132 patients met the inclusion criteria with a median age of 62 (range 36-80) and median follow-up of 28 months (range 4-128). The majority of patients had T3 (82%), N1 (64%), or M0/M1a (92%) disease. At the time of last follow-up there were a total of 6 (4.5%) local, 13 (10%) regional nodal, and 32 (23.5%) distant failures. Local failure was correlated with fewer lymph nodes assessed (p=0.01) and close or positive margins (p<0.01). Regional nodal failure was correlated with fewer lymph nodes assessed (p<0.01) and smaller pre-treatment tumor size (p=0.04). Distant recurrence was correlated with post-treatment nodal stage (p<0.01), peri-neural invasion (p=0.03), negative margins (p=0.02), ulceration (p=0.02), incomplete response (p<0.01), post-treatment PET SUV (p=0.05), 3D-CRT (0.053), metastatic disease at diagnosis (p<0.01) and post-treatment metastatic disease (p<0.01). No other patient, tumor, or treatment factor was correlated with treatment failure. Conclusions: Per our bi-institutional experience, patient, tumor, and treatment factors may predict for failure in patients undergoing tri-modality therapy for locally advanced esophageal cancer. Further data is needed to identify patterns of failure in these patients.

scholarly journals Comparison between Intensity-Modulated Radiotherapy and Three-Dimensional Conformal Radiotherapy for Their Effectiveness in Esophageal Cancer Treatment: A Retrospective Single Institution Study

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Xing-hua Bai ◽  
Jun Dang ◽  
Zhi-qin Chen ◽  
Zheng He ◽  
Guang Li
Keyword(s):  
Esophageal Cancer ◽  
Radiation Therapy ◽  
Locally Advanced ◽  
Three Dimensional ◽  
Intensity Modulated Radiotherapy ◽  
Conformal Radiotherapy ◽  
Intensity Modulated ◽  
Three Dimensional Conformal Radiotherapy ◽  
3D Crt

Although a large number of influential studies that have been conducted worldwide on locally advanced esophageal cancer (EC) have employed the treatment modality of three-dimensional conformal radiotherapy (3D-CRT), an advanced as well as highly conformal technology known as intensity-modulated radiotherapy (IMRT) has attracted increasing attention from the radiotherapy research community. This is because of the clear advantages of IMRT, including decrease in radiation dose that reaches critical cardiopulmonary organs. These two treatment modalities need to be investigated with regard to their effect on local control rate and patient survival. In addition, related clinical factors also need to be explored. Data from a total of 431 patients with locally advanced EC, who underwent radiation therapy between January 1, 2010 and December 31, 2013, were included in the present study. Two hundred and ninety-three patients received 3D-CRT, while 138 patients received IMRT. We constructed propensity score matches to make the two groups be comparable (136 patients in 3D-CRT group and 138 patients in IMRT group. Kaplan–Meier analysis was conducted to evaluate the endpoint of overall survival (OS). A Cox proportional hazards model was employed to analyze the relationship between the associated factors and the outcomes via univariate and multivariate approaches. The mean follow-up period was 36.2 months, and the median follow-up period was 23 months. For the IMRT group, the median OS was 31 months, and the 1-, 3-, and 5-year OS rates were 70.3%, 50.0%, and 42.8%, respectively, while for the 3D-CRT group, the median OS was 22 months, and the 1-, 3-, and 5-year OS rates were 63.2%, 41.0%, and 35.4%, respectively (p<0.05). The univariate analysis revealed that quit drinking, chemotherapy, and concurrent chemotherapy were significant risk factors for the prognosis of EC (p<0.05), as well as the radiation therapy technique used (p=0.052). The multivariate analysis indicated that chemotherapy and quit drinking were independent predictive factors for OS. OS is found to be significantly better in the IMRT group, compared with that of the 3D-CRT group. Even though these outcomes need further validation, IMRT should be considered preferentially as a therapeutic option for EC, in combination with chemotherapy and persuading patients to quit drinking.

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