scholarly journals Evaluating Thresholds to Adopt Hypofractionated Preoperative Radiotherapy as Standard of Care in Sarcoma

Sarcoma ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Luca F. Valle ◽  
Nicholas Bernthal ◽  
Fritz C. Eilber ◽  
Jacob E. Shabason ◽  
Meena Bedi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Local Control ◽  
Late Toxicity ◽  
Standard Of Care ◽  
Wound Complication ◽  
Phase Iii ◽  
Routine Practice ◽  
Complication Rates ◽  
Preoperative Radiation ◽  
Electronic Survey

Introduction. Data supporting hypofractionated preoperative radiation therapy (RT) for patients with extremity and trunk soft tissue sarcoma (STS) are currently limited to phase II single-institution studies. We sought to understand the type and thresholds of clinical evidence required for experts to adopt hypofractionated RT as a standard-of-care option for patients with STS. Methods. An electronic survey was distributed to multidisciplinary sarcoma experts. The survey queried whether data from a theoretical, multi-institutional, phase II study of 5-fraction preoperative RT could change practice. Using endpoints from RTOG 0630 as a reference, the survey also queried thresholds for acceptable local control, wound complication, and late toxicity for the study protocol to be accepted as a standard-of-care option. Responses were logged from 8/27/2020 to 9/8/2020 and summarized graphically. Results. The survey response rate was 55.3% (47/85). Local control is the most important clinical outcome for sarcoma specialists when evaluating whether an RT regimen should be considered standard of care. 17% (8/47) of providers require randomized phase III evidence to consider hypofractionated preoperative RT as a standard-of-care option, whereas 10.6% (5/47) of providers already view this as a standard-of-care option. Of providers willing to change practice based on phase II data, most (78%, 29/37) would accept local control rates equivalent to or less than those in RTOG 0630, as long as the rate was higher than 85%. However, 51.3% (19/37) would require wound complication rates superior to those reported in RTOG 0630, and 46% (17/37) of respondents would accept late toxicity rates inferior to RTOG 0630. Conclusion. Consensus building is needed among clinicians regarding the type and threshold of evidence needed to evaluate hypofractionated RT as a standard-of-care option. A collaborative consortium-based approach may be the most pragmatic means for developing consensus protocols and pooling data to gradually introduce hypofractionated preoperative RT into routine practice.

NRG Oncology HN006: Randomized phase II/III trial of sentinel lymph node biopsy versus elective neck dissection for early-stage oral cavity cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS6093-TPS6093
Author(s):  
Stephen Yenzen Lai ◽  
Pedro A. Torres-Saavedra ◽  
Neal E. Dunlap ◽  
Beth Michelle Beadle ◽  
Steven S. Chang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Quality Assurance ◽  
Neck Dissection ◽  
Phase Ii ◽  
Oral Cavity Cancer ◽  
Early Stage ◽  
Standard Of Care ◽  
Phase Iii ◽  
Elective Neck Dissection ◽  
Pet Ct

TPS6093 Background: Since patients with early-stage oral cavity cancer (OCC; T1-2N0M0; AJCC 8th ed) have a 20-30% rate of occult nodal metastases despite clinical and radiographic assessment, standard of care treatment includes elective neck dissection (END). Many patients have comprehensive surgical management of the regional cervical nodal basin even though the majority of those necks (70-80%) will not contain disease. Assessment of draining first echelon lymph nodes by sentinel lymph node (SLN) biopsy (Bx), a less invasive surgical procedure, may provide an alternative to END, while potentially reducing morbidity and cost. A decisive clinical trial comparing SLN Bx versus END can focus the HNC clinical and research community and resources on establishing the standard of care for management of the neck in early-stage OCC. Methods: In order to address the efficacy of SLN Bx in this population, we recently activated an international multi-institutional phase II/III prospective trial randomizing patients to two surgical arms: SLN Bx and END. PET/CT is an integral imaging biomarker in this trial. A node-negative PET/CT study with central read is required before randomization. Patients with a positive PET/CT central result will remain in a registry to compare imaging findings with final neck pathology. Given the current evidence available regarding morbidity for SLN Bx versus END, the phase II will determine if patient-reported neck and shoulder function and related QOL at 6 months after surgery using the Neck Dissection Impairment Index (NDII) shows a signal of superiority of SLN Bx compared to END. A total of 228 randomized patients with negative PET/CT for potential evaluation of shoulder-related morbidity with difference in 6-month NDII scores (minimum important difference ³7.5; one-sided a = 0.10; 90% power) will serve as the “Go/No-Go” decision to move forward into phase III. The phase III portion is a non-inferiority (NI) trial with disease-free survival (DFS) as the primary endpoint (NI margin hazard ratio 1.34 based on a 5% absolute difference in 2-year DFS; one-sided alpha 0.05; 80% power, and an interim look for efficacy at 67% of the events based on an O’Brien-Fleming boundary). The NDII at 6 months after surgery is a hierarchical co-primary endpoint for the phase III. Target accrual of phase III is 618 PET/CT negative patients, including those randomized in phase II (297 DFS events required for the final analysis). In addition to radiotherapy and imaging credentialing, quality assurance will include central pathology review of all negative SLN Bx cases and surgeon credentialing through an education course and SLN Bx and END case review by the surgical co-chairs. A surgical quality assurance working group will review all trial SLN Bx and END outcomes. As of 02/15/21, 7 patients have been screened and 6 of the planned 228 randomized patients in phase II have been enrolled. Clinical trial information: NCT04333537.

Neoadjuvant chemotherapy for adult soft tissue sarcomas: A phase II trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10069-10069
Author(s):  
Samuel Aguiar ◽  
Fabio Oliveira Ferreira ◽  
Ranyell Spencer Sobreira Batista ◽  
Alexsander Kurowa Bressan ◽  
Celso Lopes Mello ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Soft Tissue Sarcomas ◽  
Pathological Response ◽  
Amputation Rate ◽  
Wound Complications ◽  
Complication Rates ◽  
Preoperative Radiation ◽  
Chemotherapeutic Regimen

10069 Background: Treatment of soft tissue sarcomas (STS) is characterized by high rates of local control, but poor overall survival because of distant relapses and high rates of wound complications, when preoperative radiation is used. The objective of this study was to test the effectiveness of a protocol with neoadjuvant chemotherapy for STS. Methods: A phase II single-arm prospective trial was carried out. Only adult patients with high grade extremity lesions and tumors deep and larger than 5 cm were included. A total of four cycles of chemotherapy was administered pre-operatively. The chemotherapeutic regimen was: ifosfamide – total of 9.0 g/m2 per cycle, infused in 2 hours from Day 1 to Day 5 (1.8 mg/m2/day). Half of the equivalent dose of mesna was infused 15 min pre-ifosfamide and 4 hours post-ifosfamide. Doxorubicin – total of 60mg/m2 per cycle, was infused in bolus on Day 1. Filgrastima 300 mcg, SC, was administered after the last dose of chemotherapy for 5 days. Radiation was given after surgery. Toxicity was classified by the NIH Toxicity Criteria and response was determined by the RECIST criteria. The others endpoints were the amputation and the wound-related complication rates. Results: Between January, 2005 and May, 2011, 42 patients were included. 21(50%) patients have completed the 4 cycles. Nineteen patients (45.2%) have grade 3 or 4 toxicity, and one (2.3%) death related to treatment had occurred. Between severe complications, febrile neutropenia was the most frequent. By using the RECIST criteria, we observed 10(24.5%) cases of progression, 24(58.5%) cases of stable disease, and 7(17%) partial responses. No complete clinical or radiological response was observed. In the pathological analysis of the surgical specimens, 4(9.7%) cases showed no residual disease (complete pathological response), and a total of 6 (14.6%) showed ≤ 5% of viable residual cells. The amputation rate was 4.8% (2 cases) and complications related to the wound were observed in 9 patients (21.9%). Conclusions: The protocol showed a good rate of objective and pathological response, low rate of complications related to the operative wound, and maintained an acceptable amputation rate. On the other hand, we observed high rate of progression, by RECIST criteria.

Multicenter randomized controlled phase III study of nivolumab alone or in combination with ipilimumab as immunotherapy vs standard follow-up in surgical resectable HNSCC after adjuvant therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS6095-TPS6095
Author(s):  
Chia-Jung Busch ◽  
Adrian Muenscher ◽  
Christian Stephan Betz ◽  
Volkan Dogan ◽  
Philippe Schafhausen ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Distant Metastasis ◽  
Tumor Antigens ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Late Toxicity ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival ◽  
Treatment Naïve

TPS6095 Background: Surgically treated locally advanced head and neck squamous cell carcinoma (LA HNSCC) often requires postoperative chemoradiation with high risk of acute and late toxicity. Disease-free survival (DFS) after 2 years is approximately 70%. Combining Nivolumab (N), a PD-1inhibitor, and Ipilimumab, a CTLA4 inhibitor, as maintenance therapy may improve DFS due to anti-tumor effects of immunotherapy by enhancing cross-presentation of tumor antigens. The IMSTAR HN study compares neoadjuvant N and N±I 6 months after adjuvant therapy vs the standard therapy as first-line treatment for LA HNSCC. Methods: Eligible pts are ≥18 years old with treatment-naive LA HNSCC (oral cavity, oropharynx p16-, hypopharynx, and larynx), ECOG PS ≤1, and no distant metastasis. 276 pts will be randomized (2:1) into 2 arms and approximately 10 centers in Germany will be involved. Standard of care (arm II) consists of surgical resection followed by risk-adapted adjuvant (chemo)radiation. The experimental arm I receives neoadjuvant N 3mg/kg. After treatment according to standard arm a second randomization will be performed: In arm Ia N 3mg/kg will be given every 2 weeks until progression or up to 6 months. In arm Ib I 1mg/kg will be applied additionally every 6 weeks also until progression or up to 6 months. Primary endpoints is DFS in arms I and II. Secondary endpoints: Local regional control (LRC), distant metastasis free survival (DMFS), overall survival (OS), quality of life (QoL), survival depending on PD-L1 status, comparison of arm Ia vs arm II and Ib vs. II. AEs, graded per CTCAE v4.03, are evaluated for at least 12 months after randomization. The translational program includes investigations concerning immunmodulation, mutational load in general, but also specific mutations in targets involved in immune function and antigen presentation. Recruitment started in August 2018. Clinical trial information: NCT03700905.

CARMENA: Cytoreductive nephrectomy followed by sunitinib versus sunitinib alone in metastatic renal cell carcinoma—Results of a phase III noninferiority trial.

2018 ◽  
Vol 36 (18_suppl) ◽  
pp. LBA3-LBA3 ◽  
Author(s):  
Arnaud Mejean ◽  
Bernard Escudier ◽  
Simon Thezenas ◽  
Jean-Baptiste Beauval ◽  
Lionnel Geoffroy ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Risk Groups ◽  
Phase Iii ◽  
Routine Practice ◽  
Cytoreductive Nephrectomy ◽  
Phase Iii Trial ◽  
Significance Level ◽  
Dose Adaptation ◽  
Ecog Ps

LBA3 Background: Cytoreductive nephrectomy (CN) has been the standard of care in mRCC in the past twenty years, supported by randomized and large retrospective studies. However the efficacy of targeted therapies has challenged this standard. CARMENA was designed to answer the question of whether upfront CN should continue to be performed before sunitinib. Methods: CARMENA was a randomized phase III trial. Patients (pts) with synchronous mRCC, amenable to CN, were enrolled after confirmation of clear cell histology on biopsy if PS 0-1, absence of symptomatic brain metastasis, acceptable organ function and eligible for sunitinib therapy. Pts were randomized 1:1 to either CN followed by sunitinib (arm A) or sunitinib alone (arm B), and stratified by MSKCC risk groups. Sunitinib was given at 50 mg/d, 4/6wk with dose adaptation to routine practice. In arm A, sunitinib had to start 4 to 6 wk after surgery. Primary endpoint was overall survival (OS). A total of 576 pts had to be enrolled to demonstrate non inferiority hypothesis (H0: λE/λC > 1.20), with 80% power at a 1-sided significance level of 5%. Results: 450 pts were included from 9/09 to 9/17, 226 and 224 in arm A and B, respectively. Median age was 62, ECOG-PS was 0 in 56% and 1 in 44%. MSKCC risk groups were intermediate/poor in 55.6/44.4% (arm A) and in 58.5/41.5% (arm B). In arm A, 6.7% did not have CN and 22.5% never received sunitinib. In arm B, 4.9 % never received sunitinib and 17% had secondary nephrectomy. At the time of the analysis, 326 deaths have been observed with a median follow-up of 50.9 mo. OS was not inferior in arm B, overall as well as by MSKCC risk groups (table). No difference in response rate and PFS was observed. Safety of sunitinib was as expected in both arms. Conclusions: Sunitinib alone is not inferior to CN followed by sunitinib in synchronous mRCC both in intermediate and poor MSKCC risk groups. CN should not be anymore the standard of care when medical treatment is required. Clinical trial information: NCT00930033. [Table: see text]

Perioperative trastuzumab and pertuzumab in combination with FLOT versus FLOT alone for HER2-positive resectable esophagogastric adenocarcinoma: Final results of the PETRARCA multicenter randomized phase II trial of the AIO.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4502-4502 ◽  
Author(s):  
Ralf Dieter Hofheinz ◽  
Georg Martin Haag ◽  
Thomas Jens Ettrich ◽  
Kersten Borchert ◽  
Albrecht Kretzschmar ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Of Care ◽  
Phase Iii ◽  
R0 Resection ◽  
Her2 Positive ◽  
Surgical Morbidity ◽  
Pathological Complete Remission ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Esophagogastric Adenocarcinoma

4502 Background: Perioperative FLOT is a standard of care for resectable, esophagogastric adenocarcinoma (EGA). This trial evaluates the addition of trastuzumab (tras) and pertuzumab (per) to FLOT for HER2-positive resectable patients (pts). Methods: PETRARCA is a prospective, multicenter, randomized, investigator initiated trial planned as a phase II/III investigation. We report the phase II part of this trial. Pts with HER2+ resectable EGA (≥ cT2 or cN+) were enrolled. Pts were randomized 1:1 to 4 pre- and post-operative cycles of FLOT (Docetaxel 50 mg/m²; Oxaliplatin 85 mg/m²; Leucovorin 200 mg/m²; 5-FU 2600 mg/m², q2w) (Arm A) or the same regimen with tras 8/6 mg/kg and per 840 mg q3w, followed by 9 cycles tras/per (arm B). Primary endpoint for the phase II part was the rate of pathological complete remission (pCR). Main secondary endpoints were DFS, OS and safety. Results: The trial closed prematurely and did not proceed to phase III. In total, 81 pts were randomized (A, 41; B, 40). Baseline characteristics were balanced (overall, male 79%; median age 60; cT3/T4 86%; cN+ 85%; GEJ 75%). 93% in arm A and 90% in arm B completed pre-OP treatment as planned. More pts had at least one dose modification in arm B (A, 44%; B, 70%). The pCR rate was significantly improved with tras/per (A, 12%; B, 35%; p = 0.02). Likewise, the rate of pathological lymph node negativity was higher with tras/per (A, 39%; B, 68%). R0-resection rate (A, 90%; B, 93%) and surgical morbidity (A: 43%; B, 44%) were comparable. Moreover, in-house mortality was equal in both arms (overall 2.5%). Median DFS was 26 months in arm A and not yet reached in arm B (HR 0.58, p = 0.14). After a median follow-up of 22 months median OS was not yet reached. DFS and OS rates [with 95% CI] at 24 months were 54% [38-71%] and 77% [63-90%] in arm A and 70% [55-85%] and 84% [72-96%] in arm B, respectively. In terms of toxicity more ≥ grade 3 adverse events were reported with tras/per (75% vs. 85%), especially diarrhea (5% vs. 41%) and leukopenia (13% vs 23%). Conclusions: The addition of tras/per to perioperative FLOT significantly improved pCR and nodal negativity rates in pts with Her2+ resectable esophagogastric adenocarcinoma at the price of higher rates of diarrhea and leukopenia. Clinical trial information: NCT02581462 .

scholarly journals Adjuvant Gemcitabine Alone Versus Gemcitabine-Based Chemoradiotherapy After Curative Resection for Pancreatic Cancer: A Randomized EORTC-40013-22012/FFCD-9203/GERCOR Phase II Study

2010 ◽  
Vol 28 (29) ◽  
pp. 4450-4456 ◽  
Author(s):  
Jean-Luc Van Laethem ◽  
Pascal Hammel ◽  
Françoise Mornex ◽  
David Azria ◽  
Geertjan Van Tienhoven ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Pancreatic Head ◽  
Disease Free Survival ◽  
Late Toxicity ◽  
Phase Iii ◽  
Adjuvant Chemoradiotherapy ◽  
R0 Resection ◽  
Type I ◽  
Pancreatic Head Cancer

Purpose The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer. Patients and Methods Within 8 weeks after surgery, patients were randomly assigned to receive either four cycles of gemcitabine (control arm) or gemcitabine for two cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm). The primary objective was to exclude a < 60% treatment completion and a > 40% rate of grade 4 hematologic or GI toxicity in the CRT arm with type I and II errors of 10%. Secondary end points were late toxicity, disease-free survival (DFS), and overall survival (OS). Results Between September 2004 and January 2007, 90 patients were randomly assigned (45:45). Patient characteristics were similar in both arms. Treatment was completed per protocol by 86.7% and 73.3% (80% CI, 63.1% to 81.9%; 95% CI, 58.1% to 85.4%) in the control and CRT arms, respectively, and grade 4 toxicity was 0% and 4.7% (two of 43; 80% CI, 1.2% to 11.9%), respectively. In the CRT arm, three patients experienced grade 3–related late toxicity. Median DFS was 12 months in the CRT arm and 11 months in the control arm. Median OS was 24 months in both arms. First local recurrence was less frequent in the CRT arm (11% v 24%). Conclusion Adjuvant gemcitabine-based CRT is feasible, well-tolerated, and not deleterious; adding this treatment to full-dose adjuvant gemcitabine after resection of pancreatic cancer should be evaluated in a phase III trial.

Evaluation of Early and Late Toxicities in Chemoradiation Trials

2007 ◽  
Vol 25 (26) ◽  
pp. 4096-4103 ◽  
Author(s):  
Søren M. Bentzen ◽  
Andrea Trotti
Keyword(s):  
Adverse Effects ◽  
Tissue Injury ◽  
Late Toxicity ◽  
Standard Of Care ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Randomized Controlled ◽  
Solid Malignancies ◽  
Phase Iii Trials ◽  
Low Incidence

Combined chemoradiotherapy is increasingly becoming a standard of care for the nonoperative management of a variety of solid malignancies. A string of randomized controlled phase III trials have shown statistically significant and clinically relevant improvements in outcome, ostensibly without any apparent increase in late toxicity. However, the reliability and the sensitivity of toxicity reporting in most trials are questionable. Audits and phase IV studies suggest that the chemoradiotherapy success comes at a price in terms of late toxicity. This review presents some of the challenges in recording, analyzing, and reporting toxicity data. Methods for summarizing toxicity are reviewed, and a new investigational metric, the TAME reporting system, is discussed. The need for special vigilance in the era of molecular-targeted agents is emphasized because of the possibility that unexpected serious adverse events with a low incidence may occur. Finally, we discuss how progress in molecular pathology and radiation biology may provide novel opportunities for stratifying patients according to risk of adverse effects, interventional targets for reducing or treating adverse effects, and surrogate markers of normal-tissue injury.

scholarly journals Optimizing Treatment for Head and Neck Cancers: Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

2020 ◽  
Vol 18 (7.5) ◽  
pp. 982-984
Author(s):  
Robert I. Haddad
Keyword(s):  
Head And Neck ◽  
Single Agent ◽  
Standard Of Care ◽  
Phase Iii ◽  
Routine Practice ◽  
Second Line ◽  
First Line ◽  
Positive Score ◽  
Combined Positive Score ◽  
Line Setting

Immunotherapy has changed the game in the treatment of head and neck cancer (HNC). Practice-changing results from the phase III KEYNOTE-048 trial led to the approval of pembrolizumab immunotherapy alone or in combination with chemotherapy for the treatment of recurrent/metastatic HNC in the first-line setting. Testing for combined positive score (CPS) is now part of routine practice, because patients with CPS ≥1 can be started on single-agent immunotherapy in the first-line. Pembrolizumab replaces the “old” standard of care established by the EXTREME study, as trials looking at targets besides immunotherapy have proved “disappointing.” Additionally, nivolumab and pembrolizumab are both approved for use in the second-line.

BC2001: A multicenter phase III randomized trial of standard versus reduced volume radiotherapy for muscle invasive bladder cancer (ISCRTN:68324339)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5022-5022
Author(s):  
R. A. Huddart ◽  
N. D. James ◽  
F. Adab ◽  
I. Syndikus ◽  
P. Jenkins ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Local Control ◽  
Late Toxicity ◽  
Phase Iii ◽  
Invasive Bladder Cancer ◽  
Target Dose ◽  
Muscle Invasive Bladder Cancer ◽  
Tumour Control ◽  
Reduced Volume ◽  
Muscle Invasive

5022 Background: Radiotherapy (RT) is an alternative to radical cystectomy in the management of muscle invasive bladder cancer. Limitations are probability of attaining and maintaining local tumour control and risk of late bladder toxicity. BC2001 tests whether concomitant chemotherapy (CT) improves loco-regional control and whether RT volume modification reduces late toxicity without detriment to tumour control. Methods: Pts were randomized in a 2x2 factorial design to (i) RT vs RT + concomitant CT (5FU 500mg/m2 d1–5 wks 1 & 4 + mitomycin C 12mg/m2 d1) and/or (ii) standard RT to tumour and whole bladder with 1.5cm margin (sRT) vs reduced volume RT (rvRT) where tumour + 1.5cm margin was treated to 100(±5)% target dose and remaining bladder received 80% target dose. RT dose was 55Gy/20F or 64Gy/32F according to local practice. RT volume comparison results (primary endpoint RTOG toxicity at 1 yr) are reported. Target sample size was 480 pts but the RT randomisation closed early due to slow recruitment. Estimated power is 73% (two-sided α = 0.05) to detect a 20% difference in G3/4 toxicity. Results: 219 pts were recruited (108 sRT; 111 rvRT); 49 received neoadjuvant CT; 31 sRT and 33 rvRT were randomised to concomitant CT. Median age was 74 yrs. Median follow up is 36 mths. There was no difference in loco-regional disease-free survival (LRDFS: HR = 1.06, 95% CI: 0.62–1.84) nor overall survival (HR = 0.99, (0.61 - 1.35)) between randomised RT groups. 2yr LRDFS is 71% in both RT groups. 27 (16) sRT vs 32 (15) rvRT pts have had local (invasive) recurrences (p = 0.09); 32 pts have undergone salvage cystectomy. No difference was seen in CTC G3/4 acute toxicity (26% sRT vs 21% rvRT, p = 0.35), RTOG G3/4 toxicity at 12 mths (8% sRT vs 4% rvRT, p = 0.27) nor Lent Som G3/4 toxicity at 12 mths (45% sRT vs 34% rvRT, p = 0.21). Bladder capacity fell significantly in sRT group (mean reduction at 12 mths: 59mls, 95%CI: 47–118mls, p = 0.02) but not in rvRT group. Conclusions: RT in the modern era can attain local control in most patients with T2-T3 bladder cancer. Acute and late toxicity was less than anticipated in both treatment groups. Modifying standard RT volumes had minimal effect on local control and toxicity in this trial. 2 yr toxicity and quality of life data will be presented. No significant financial relationships to disclose.

A multi-institutional phase II study of high-dose hypofractionated proton beam therapy (HF-PBT) for unresectable primary liver cancers: Long-term outcomes in patients (pts) with hepatocellular carcinoma (HCC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 376-376
Author(s):  
Theodore S. Hong ◽  
Jennifer Yon-Li Wo ◽  
Edgar Ben-Josef ◽  
Erin McDonnell ◽  
Lorraine C. Drapek ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Proton Beam ◽  
Phase Ii ◽  
Local Control ◽  
Phase Ii Study ◽  
Proton Beam Therapy ◽  
Post Treatment ◽  
Phase Iii ◽  
High Dose

376 Background: Retrospective reports of PBT in hepatocellular carcinoma (HCC) demonstrate local control (LC) rates exceeding 85%. We prospectively replicate these findings and explore predictors of overall survival (OS) in pts with unresectable HCC receiving high dose, HF-PBT. Methods: Pts were enrolled on an NCI sponsored, multi-institutional, phase II study (NCT00976898). Key eligibility were unresectable HCC; Child’s A/B; ECOG PS 0-2; no extrahepatic disease; no prior RT. Maximum tumor size was 12 cm if solitary, 10 cm if 2 tumors, and 6 cm if 3. PBT was given in 15 fractions to a maximum total dose of 67.5 GyE. Sample size was calculated to demonstrate > 80% LC at 2 yrs (LC-2). Results: From 2009-2015, 44 patients were treated. Median age was 70 years (53-89) and 37 (84.1%) were male. 35 (79.5%) pts had Child A or no cirrhosis. 32 (72.7%) pts had 1 tumor, 12 (27.2%) had multiple tumors. Median longest tumor dimension was 5.0 cm (range 1.9-12.0). Median baseline AFP was 18.6 ng/mL (range 1.3-66081) and 29 pts (67.4%) had elevated AFP ( > 7.9 ng/mL). Median RT dose delivered was 58.0 GyE (range 40.5-67.5). 1 pt (2%) had grade 3 RT related toxicity (thrombocytopenia). With a median follow up 21.8 mo among 28 survivors, the LC-2 was 94.8% (95% CI 84.5-99.1%). mOS was 49.9 mo (95% CI 17.8 months- upper limit not reached) and mPFS was 13.9 mo (95% CI 8.4-49.9). OS did not differ by CLIP score, PS, prior treatment, vascular thrombus, baseline AFP, size, or dose. Median AFP change from baseline to 3 mo post treatment was a 32.8% reduction. Median time to AFP nadir in pts with elevated baseline levels was 3.9 mo (0-30.5). % decrease in AFP from baseline to 6 mo post-treatment was significantly associated with lower hazard of death. (HR = 0.993, p = 0.016). Conclusions: High dose hypofractionated proton beam therapy demonstrated a high local control rate for HCC with favorable safety profiles, supporting the ongoing evaluation of radiation in HCC in phase III studies. AFP decrease from baseline to 6 months post-radiation is associated with improved overall survival. Clinical trial information: NCT00976898.

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