Proton radiotherapy for rhabomyosarcoma: Preliminary results from a multicenter prospective study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9585-9585
Author(s):  
Torunn I. Yock ◽  
Jackie Szymonifka ◽  
Alison M. Friedmann ◽  
Anita Mahajan ◽  
Beow Yong Yeap ◽  
...  
Keyword(s):  
Late Effects ◽  
Prospective Trial ◽  
Progression Free Survival ◽  
Stage I ◽  
Entire Group ◽  
Early Results ◽  
Group I ◽  
Oral Pain ◽  
Grade 3

9585 Background: Pediatric rhabdomyosarcoma (RMS) is commonly cured with chemotherapy and radiation. However, late effects of radiotherapy (RT) can be disabling. Proton RT irradiates less normal tissue, which should result in fewer late side effects of treatment. The purpose of this study was to describe the disease control and side effect profile of proton RT in RMS patients (pts). Methods: Eligible pts included those with localized disease and metastatic embryonal RMS if age 2-10. All pts were treated with VAC (vincristine, actinomycin, cyclophosphamide) based chemotherapy and proton RT, median dose 50.4 Gy (36-50.4 GyRBE). Concurrent enrollment in COG protocols was allowed. All pathology/imaging was reviewed at the treating institution. Results: 47 pts with RMS were prospectively enrolled from January 2005 to June 2011 and evaluable for analysis. Median age was 3.1 yrs, (range 0.6-15.6 years; M/F ratio 23:24). There were 1, 7, 37, and 2 Group I, II, III and IV and 14, 12, 19 and 2, Stage I-IV pts respectively, and 33 with embryonal 14 with alveolar/other. Most common sites included PM (48.9%), orbital (23.4%) bladder/prostate (6.4%), H&N non-PM (6.4%), extremities (4.3%), trunk/abdomen 2.1%), perineal/anal region (2.1%) and other (6.4%). Median follow-up is 15.2 months. One/two-year overall survival (OS) and progression-free survival (PFS) for the entire group is 94/81% (OS) and 79/73% (PFS). 2-year OS for stage I,II/III,IV pts is 91/66% (OS, p=0.114) and two-year PFS for these pts is 86/57%, respectively, (p=0.083. 16 (34%) had grade 3/4 acute toxicities attributable to the radiation during treatment, the most common of which was mucositis/oral pain (12.8%), anorexia (4.3%), and erythema (4.3%). Among the 24 pts analyzable for late toxicities with at least 2 yrs of follow up, there were no grade 3 or 4 late toxicities attributable to radiation. Conclusions: Early results of this prospective trial demonstrate comparable disease outcomes and thus far limited late effects in a young pediatric RMS population. However, additional follow up is needed to determine if protons truly reduce rates and severity of late effects compared with photon cohorts published in the literature.

A phase II trial of proton radiotherapy for medulloblastoma: Preliminary results.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. CRA9507-CRA9507 ◽  
Author(s):  
T. I. Yock ◽  
B. Y. Yeap ◽  
D. Ebb ◽  
S. M. MacDonald ◽  
M. B. Pulsifer ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Late Effects ◽  
Prospective Trial ◽  
Hormone Deficiency ◽  
Entire Group ◽  
Proton Radiotherapy ◽  
Early Results ◽  
Pediatric Medulloblastoma ◽  
Platinum Based Chemotherapy

CRA9507 Background: Pediatric medulloblastoma (MB) is commonly cured with surgery, chemotherapy and radiation. However, the late effects of radiotherapy can be disabling. Proton radiotherapy irradiates less normal tissue, which should result in fewer late side effects of treatment. The purpose of this study was to describe the clinical outcomes of proton radiotherapy. Methods: All patients had surgery of the primary tumor followed by proton radiotherapy with or without concurrent chemotherapy and adjuvant platinum based chemotherapy. CSI doses ranged from 18-36 GyE, median dose 23.4 GyE. The tumor bed or posterior fossa was brought to 54 GyE. Concurrent enrollment in COG or other protocols was allowed. All pathology and imaging was reviewed at MGH to confirm the diagnosis. Results: 60 patients with MB were prospectively enrolled from May 2003 to December 2009 and 59 were evaluable for this analysis. Median age 6.6 yrs, range 3.5 - 22 years; M/F ratio 1.3; standard risk (SR, 45) or high risk (HR, 14). The median follow-up is 16 months. Two-year overall survival (OS) and progression-free survival (PFS) for the entire group is 91% and 87%. Two-year OS for SR MB and HR MB is 92% and 87%. 54 pts have baseline (BL) neurocognitive testing and 19 pts (14 SR, 5 HR) have follow-up (FU) evaluations including FSIQ spanning at an average of 2 years. Mean FSIQ at BL and FU are 107 and 102 (paired t-test: 0.046). Endocrine late effects include 4 patients with growth hormone deficiency, 1 patient with central hypothyroidism and 2 other endocrinopathies. Audiology information will be presented. Conclusions: Early results of this prospective trial are promising for improving clinical outcomes in patients with medulloblastoma. [Table: see text]

Fractionated Stereotactic Radiotherapy for Pituitary Adenomas

Neurosurgery ◽  
2015 ◽  
Vol 79 (3) ◽  
pp. 406-417 ◽  
Author(s):  
Sean M. Barber ◽  
Bin S. Teh ◽  
David S. Baskin
Keyword(s):  
Stereotactic Radiotherapy ◽  
Pituitary Adenomas ◽  
Progression Free Survival ◽  
Hormonal Control ◽  
Fractionated Stereotactic Radiotherapy ◽  
Small Series ◽  
Early Results ◽  
Nonfunctional Pituitary Adenomas

Abstract BACKGROUND Early results of postoperative fractionated stereotactic radiotherapy (FSRT) for functional and nonfunctional pituitary adenomas appear promising, but the majority of available evidence draws from small series with insufficient follow-up data to draw meaningful conclusions. OBJECTIVE To evaluate the long-term outcomes of a large series of patients undergoing FSRT for both functional and nonfunctional pituitary adenomas with the Novalis system (Brain LAB, Heimstetten, Germany). METHODS Chart data for 75 consecutive patients undergoing FSRT for a pituitary tumor (21 functional and 54 nonfunctional adenomas) at our institution between January 2004 and June 2013 were reviewed. RESULTS Radiographic progression-free survival was 100% over a mean of 47.8 months of radiographic follow-up (range, 12.0-131.2 months). Hormonal normalization was seen in 69.2% of patients with functional adenomas after FSRT, whereas 30.8% experienced partial hormonal control. Mild, grade I acute adverse effects were observed during radiotherapy treatment in 36 patients (48%), and objective, persistent worsening of vision occurred in a single patient (1.5%) after FSRT. New hormonal deficits were seen in 28.0% of patients after FSRT. Radiographic responses were inversely related to tumor volume. CONCLUSION FSRT delivers radiographic and functional outcomes similar to those seen with stereotactic radiosurgery and conventional radiotherapy with less resultant toxicity. FSRT is most beneficial for smaller tumors (those <3 cm in diameter).

scholarly journals FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

2021 ◽  
Author(s):  
Jane E. Rogers ◽  
Michael Lam ◽  
Daniel M. Halperin ◽  
Cecile G. Dagohoy ◽  
James C. Yao ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Prior Therapy ◽  
Well Differentiated ◽  
Grade 3 ◽  
Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9000-9000
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Expression Level ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

scholarly journals Stereotactic Body Radiotherapy for Metastatic and Recurrent Soft Tissue Sarcoma

2020 ◽  
Author(s):  
Xiaoyao Feng ◽  
Jing Li ◽  
Aomei Li ◽  
Han Zhou ◽  
Xixu Zhu ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Hematogenous Metastasis ◽  
Invasive Growth ◽  
Free Survival ◽  
Grade 3 ◽  
Clinical Transformation

Abstract BackgroundSoft tissue sarcoma（STS） is a malignant tumor of highly heterogeneous mesenchymal origin. STS has a biologic pattern and clinical transformation with localized invasive growth and susceptibility to hematogenous metastasis. Metastatic and recurrent soft tissue sarcoma may be treated by local therapeutic options, including surgery and radiation therapy. This study evaluated the safety and efficacy of SBRT for metastatic and recurrent soft tissue sarcoma.MethodsWe performed a retrospective analysis of 37 STS patients with 58 lesions treated with SBRT from 2009-2019 at our institution. We analyze the local control (LC), overall survival (OS), progression free survival (PFS) and toxicity rates of the patients.ResultThe median follow-up was 20 months（range 2 to 120 months）. One and two year LC rates were 75.3% and 55.2% [95% confidence interval (CI) 20–25 months]. Median OS was 24 months and the survival rates were 66.6%, 45% and 26.6% at 1, 2 and 3-year after SBRT. Median PFS were 11months (95% CI 8–18 months). No acute or chronic grade ≥ 3 toxicity was observed.ConclusionsIn patients with metastatic and recurrent STS, LC, OS and PFS were higher than expected. SBRT should be a proper treatment option for STS.

scholarly journals Shortened Immunosuppression Following Peripheral Blood (PB) Haploidentical (haplo) Transplantation with Post-Transplant Cyclophosphamide (PTCy) Is Associated with Tolerable Rates of Graft-Vs-Host Disease (GVHD)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3320-3320
Author(s):  
Amy E. DeZern ◽  
Marianna Zahurak ◽  
Javier Bolanos-Meade ◽  
Richard J. Jones
Keyword(s):  
Graft Failure ◽  
Acute Gvhd ◽  
Risk Index ◽  
Chronic Gvhd ◽  
Prospective Trial ◽  
Stopping Rules ◽  
High Dose ◽  
Gvhd Prophylaxis ◽  
Grade 3

With PTCy as GVHD prophylaxis, nonmyeloablative (NMA) HLA- haplo and HLA-matched blood or marrow (BMT) have comparable outcomes. Previous reports showed that discontinuation of immunosuppression (IST) as early as day 60 after infusion of bone marrow (BM) haplo allograft with PTCy is feasible. However, there are certain diseases in which PB may be favored over BM grafts to augment engraftment rates; however, given the higher rates of GVHD with PB, excessive GVHD becomes a concern with early discontinuation of IST. We present a completed, prospective single-center trial of stopping IST at days 90 and 60 after NMA haplo PB. (NCT02556931) From 12/2015-7/2018, 117 evaluable patients (pts) with hematologic malignancies associated with higher rates of graft failure with PTCy (MDS, MPN, overlap syndromes, 2o AML, AML with MRD, MM, and CLL) received NMA PB allografts on trial. Haplo donors were preferred, but in patients lacking suitable haplo relatives, unrelated donors were employed with 6 in each IST cohort. The primary objective was to evaluate the safety and feasibility of reduced‐duration IST (from Day 5 through Day 90 in cohort 1 and through Day 60 in cohort 2.) Transplant inclusion criteria were standard and the conditioning included Cy (14.5 mg/kg IV D -6 and -5), fludarabine (D -6 to -2), TBI (200 cGy D -1) and T-cell replete PB. GVHD prophylaxis consisted of high-dose PTCy (50 mg/kg IV D 3 and 4), mycophenolate mofetil (D 5-35) and IST (tacrolimus/sirolimus) from D 5 forward. Priot to transplantation, pts were assigned to stop IST early if eligible, as defined by having ≥ 5% donor T cells at ~D 56 onward, no relapse, and no grade 2-4 acute or significant chronic GVHD. If ineligible to discontinue IST early, it continued through D 180. Monitoring rules declared reduced IST feasible if ≥ 33% of pts stopped IST early as planned. Safety stopping rules for early IST cessation were based on ≥ 5% graft failure, ≥ 5% NRM, ≥ 50% relapse, and ≥ 10% combined grade 3-4 acute GVHD and severe chronic GVHD, measured from the IST stop date to ~D 180. Historical data from 55 haplo transplants for MDS, CLL, and MPNs at our center using the same regimen and PB grafts informed safety calculations. Of the 117 pts (median age 64 years, range 24-78), the most common diagnoses were MDS (33%), AML (with MRD or arising from antecedent disorder) (31%), MPNs (21%) myeloma (10%), and CLL (6%). By refined Disease Risk Index, 13% were low risk, 69% intermediate and 18% high. Shortened IST was feasible in 75 pts (64%) overall. Ineligibility for shortened IST was due most commonly to GVHD (17 pts), followed by early relapse (11 pts), NRM (7 pts), patient/ physician preference (4 pts) or graft failure (3 pts). Of the 57 patients in the D90 cohort (median follow up 35 mos), 33 (58%) stopped IST early as planned. Of the 60 patients in the D60 cohort (median follow up 20 mos), 42 (70%) stopped IST early as planned. The graft failure rate was 2.6%. NRM was very similar in the two arms, 12% at both 12 and 18 months in the D90 cohort and 10% and 13% at 12 and 18 months in the D60 cohort. Relapse in D90 cohort is 40% at 18 months compared to 33% at 18 months in the D60 cohort. Figure 1 shows cumulative incidence (CI) of acute grade 2-4 and grade 3-4 GVHD. Although the CI of grade 1-2 GVHD may be slightly higher in day 60 cohort, it is only 40% at D180. Severe chronic GVHD was 12% (D90) and 11% (D60) at 540 days. One year OS is 75% and 78% for the D90 and D60 cohorts, respectively. At 12 months PFS is 54% in the D90 group and 67% in the D60. At 12 months, the GRFS is 33% in the D90 group, and 38% in the D60 group. (Figure 2) These data suggest that reduced-duration IST in pts receiving NMA haplo PB with PTCy is feasible and carries an acceptable safety profile. Risks of acute GVHD, chronic GVHD, graft failure and NRM appear similar to historical outcomes with IST until D180 and between the two cohorts. When comparing the D90 and D60 arms, grade 3-4, severe chronic GVHD, GRFS, OS and PFS were similar. Although a larger, prospective trial would be needed to uncover potential small differences in outcomes based on IST duration, these data show that similar to our findings with BM, many PB pts (64% in this trial) can discontinue IST as early as D60 without undue toxicity. The favorable toxicity profile of the PTCy platform, coupled with the feasibility and safety of early IST cessation, provides an ideal setting to incorporate novel post-transplantation approaches for relapse reduction. Figure 1 Disclosures DeZern: Astex Pharmaceuticals, Inc.: Consultancy; Celgene: Consultancy. Bolanos-Meade:Incyte Corporation: Other: DSMB fees.

scholarly journals Time to Progression Post-Induction Predicts Outcomes of Ixazomib Based Therapy for Relapsed/Refractory Myeloma: Real World Data from a Multi-Site Israeli Registry Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1972-1972
Author(s):  
Yael C Cohen ◽  
Hila Magen ◽  
Noa Lavi ◽  
Moshe E. Gatt ◽  
Evgeni Chubar ◽  
...  
Keyword(s):  
Research Funding ◽  
Overall Response Rate ◽  
Target Organ Damage ◽  
Progression Free Survival ◽  
Organ Damage ◽  
Real World Data ◽  
Free Survival ◽  
Grade 3 ◽  
Indolent Disease

Abstract Introduction Ixazomib is an orally available proteasome inhibitor, shown to be safe and efficacious in combination with lenalidomide and dexamethasone (IRd regimen) in patients with relapsed and refractory multiple myeloma (RRMM) with 1-3 prior lines, demonstrating a progression free survival (PFS) benefit which was similar across cytogenetic risk groups (Tourmaline-MM1 phase 3 trial). A European real world data analysis of an IRd named patient program (NPP) outcomes in Greece (n=35), UK (n=46) and Check republic (n=57) showed similar favorable outcomes (Terpos et al, Blood 2017 130:3087). We aimed to analyze outcomes of ixazomib combinations among a multi-site cohort in the Israeli Myeloma registry. Overall response rate (ORR) was classified according to IMWG criteria. Primary endpoint was PFS, secondary endpoints included ORR, overall survival (OS), safety and tolerability. Patients A total of 78 patients across 7 sites, who received at least one cycle of ixazomib combination between June 2013 and June 2018 for treatment of RRMM were retrospectively included. Median age was 68 (range: 38-90). Male/Female ratio was 42/36. ISS (rISS) I/II/II was 30%/42%/27% (25%/54%/15%). Patient received between 1 and 7 prior lines of therapy, 66% received ixazomib in 2nd line, 18% in 3rd line. Overall, 89% of patients had been exposed to PIs (bortezomib 86%) prior to IRd, 41% to IMiDs (thalidomide 28% lenalidomide 22% and pomalidomide 6%), and 35% had undergone autologous transplantation (ASCT). Induction treatment was mostly bortezomib based (85%), most frequently VCD (62%). FISH cytogenetics were available for 60 patients, 29 (48%) had high or intermediate risk aberrations (t(4:14) 12 pts, amp 1q21 12 pts, del17p 9 pts). Disease aggressiveness was classified by treating physician as indolent (rapid control to protect from target organ damage not required) vs aggressive (imminent target organ damage) in 63% vs 27%, respectively. 60 (77%) of the 78 patients received ixazomib via a named patient program, the rest via national or private healthcare provider. Results Median time of follow up from first ixazomib dose was 22 months (range: 1-39 months), and 54 months from diagnosis of myeloma. Treatment is ongoing in 44 (56%) patients with a median duration of 19 months (range: 1-29). Among patients who discontinued treatment, the median duration was 9 months (1-31). Ixazomib was combined with lenalidomide, pomalidomide, and daratumumab in 69%, 9% and 4%, respectively. Overall response rate was 88% - CR 10%, VGPR 36%, PR 42%. Progression free survival was 78% and 54% at 12 and 24 months, respectively (fig1a). A worse PFS was found with physician assessment of aggressive vs indolent disease (14.5 vs 25.9 months, p=0.001), and with post induction progression free period (PFS1) ≤ 24 months vs. >24 months (23.9 vs 31.5 months, p=0.038) (fig 1b); age >=65 trended towards a worse PFS (p=0.058). Poor cytogenetic risk, prior exposure to bortezomib, prior auto transplant, and number of prior lines of therapy did not affect PFS or ORR. OS from first ixazomib administration was 90% and 81% at 12 and 24 months, respectively; median OS was not reached (fig1a). Any (grade 3-4) toxicity considered by investigator as related to ixazomib was reported in 70% (18% grade 3-4), including neutropenia 14% (6%), anemia 19% (6%), thrombocytopenia 17% (5%), nausea and vomiting 17% (1%), DVT/PE 4% (1%), neutropenic infection 0 (4%), peripheral neuropathy 14% (3%), diarrhea 14% (3%), rash 10% (4%), pneumonia 5% (3%). There were no ixazomib related deaths. Dose reduction or discontinuation due to toxicity occurred in 28% and 12%, respectively. Conclusion Our data shows ixazomib-based combinations are efficacious and safe regimens for patients with RRMM, achieving ORR of 88%, at 2nd as well as later lines of therapy, regardless to cytogenetic risk. Over a median follow up of almost 2-years, 54% remained progression free at 24 months. An ixazomib based regimen may be particularly attractive for patients who remain progression free for more than 24 months after a bortezomib induction and for patients with a more indolent disease phenotype. Disclosures Cohen: Neopharm Israel: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Medisson Israel: Consultancy, Honoraria, Research Funding. Tadmor:NOVARTIS: Consultancy; PFIEZER: Consultancy; ABBVIE: Consultancy; JNJ: Consultancy; ROCHE: Research Funding.

Adaptive Dosing of Nivolumab + Ipilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study)

2021 ◽  
Author(s):  
Michael A. Postow ◽  
Debra A. Goldman ◽  
Alexander N. Shoushtari ◽  
Allison Betof Warner ◽  
Margaret K. Callahan ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Computed Tomography Scan ◽  
Free Survival ◽  
Immunotherapy Trial ◽  
Grade 3 ◽  
Almost All ◽  
Tomography Scan

PURPOSE Nivolumab + ipilimumab (nivo + ipi) is highly efficacious but has high toxicity. Standard treatment in advanced melanoma is four doses of nivo + ipi followed by nivo alone. Whether four doses of nivo + ipi are needed is unclear. METHODS The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT) study ( NCT03122522 ) is a multicenter, single-arm phase II clinical trial. Patients received two doses of nivo (1 mg/kg) + ipi (3 mg/kg) followed by a computed tomography scan at week 6. Patients without new lesions or index lesion tumor growth of > 4% had protocol-defined early favorable antitumor effect (FATE) and ceased nivo + ipi, transitioning to nivo monotherapy. Patients without FATE at week 6 received the standard third and fourth doses of nivo + ipi followed by nivo monotherapy. The primary end point was response rate by RECIST 1.1 at week 12. Secondary end points included additional efficacy assessments and safety. RESULTS Sixty patients were enrolled; 41 patients (68%) had FATE at week 6 and met criteria for stopping nivo + ipi. Best overall response rates by RECIST at week 12 or any time afterward were 48% (95% CI, 35 to 62) and 58% (95% CI, 45 to 71), respectively. With a median follow-up of 25 months, the estimated 18-month progression-free survival and overall survival are 52% and 80%, respectively. Fifty seven percent of patients had grade 3-5 treatment-related toxicity. CONCLUSION The efficacy and toxicity of standard four dose nivo + ipi induction therapy in melanoma is likely driven by the first two doses. An interim computed tomography scan after two doses guided cessation of combination dosing and identified almost all responders. Longer follow-up and further study are needed to fully understand the implications of a shortened induction course of nivo + ipi.

Five-Year Outcomes of Stereotactic Body Radiation Therapy (SBRT) for Prostate Cancer-The Largest Experience in China

2021 ◽  
Author(s):  
Xianzhi Zhao ◽  
Yusheng Ye ◽  
Haiyan Yu ◽  
Lingong Jiang ◽  
Chao Cheng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Cox Regression Analysis ◽  
Gu Toxicity ◽  
Biochemical Progression ◽  
Grade 3 ◽  
Very High

Abstract Objective To evaluate the efficacy and toxicity of SBRT for localized prostate cancer (PCa). Moreover, it is the largest-to-date pilot study to report 5-year outcomes of SBRT for localized PCa from China. Methods In this retrospective study, 133 PCa patients in our center were treated by SBRT with CyberKnife (Accuray) from October 2012 to July 2019. Follow-up was performed every 3 months for evaluations of efficacy and toxicity. Biochemical progression-free survival (bPFS) and toxicities were assessed using the Phoenix definition and the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 respectively. Factors predictive of bPFS were identified with COX regression analysis. Results 133 patients (10 low-, 21 favorable intermediate-, 31 unfavorable intermediate-, 45 high-, and 26 very high risk cases on the basis of the NCCN risk classification) with a median age of 76 years (range: 54–87 years) received SBRT. The median dose was 36.25Gy (range: 34-37.5Gy) in 5 fractions. Median follow-up time was 57.7 months (3.5–97.2 months). The overall 5-year bPFS rate was 83.6% for all patients. The 5-year bPFS rate of patients with low-, favorable intermediate-, unfavorable intermediate-, high-, and very high risk PCa was 87.5%, 95.2%, 90.5%, 86.3%, and 61.6% respectively. Urinary symptoms were all alleviated after SBRT. All the patients tolerated SBRT with only 1 (0.8%) and 1 (0.8%) patient reporting grade-3 acute and late genitourinary (GU) toxicity, respectively. There were no grade 4 toxicities. Gleason score (P < 0.001, HR = 7.483, 95%CI: 2.686–20.846) was the independent predictor of bPFS rate after multivariate analysis Conclusion SBRT is an efficient and safe treatment modality for localized PCa with high 5-year bPFS rates and acceptable toxicities.

Results of a Prospective Trial of Mantle Irradiation Alone for Selected Patients With Early-Stage Hodgkin’s Disease

2001 ◽  
Vol 19 (3) ◽  
pp. 736-741 ◽  
Author(s):  
Kendall H. Backstrand ◽  
Andrea K. Ng ◽  
Ronald W. Takvorian ◽  
Ellen L. Jones ◽  
David C. Fisher ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Early Stage ◽  
Hodgkin’S Disease ◽  
Clinical Stage ◽  
Prospective Trial ◽  
Stage I ◽  
Mixed Cellularity ◽  
European Organization ◽  
Extended Field

PURPOSE: To determine the efficacy of mantle radiation therapy alone in selected patients with early-stage Hodgkin’s disease. PATIENTS AND METHODS: Between October 1988 and June 2000, 87 selected patients with pathologic stage (PS) IA to IIA or clinical stage (CS) IA Hodgkin’s disease were entered onto a single-arm prospective trial of treatment with mantle irradiation alone. Eighty-three of 87 patients had ≥ 1 year of follow-up after completion of mantle irradiation and were included for analysis in this study. Thirty-seven patients had PS IA, 40 had PS IIA, and six had CS IA disease. Histologic distribution was as follows: nodular sclerosis (n = 64), lymphocyte predominant (n = 15), mixed cellularity (n = 3), and unclassified (n = 1). Median follow-up time was 61 months. RESULTS: The 5-year actuarial rates of freedom from treatment failure (FFTF) and overall survival were 86% and 100%, respectively. Eleven of 83 patients relapsed at a median time of 27 months. Nine of the 11 relapses contained at least a component below the diaphragm. All 11 patients who developed recurrent disease were alive without evidence of Hodgkin’s disease at the time of last follow-up. The 5-year FFTF in the 43 stage I patients was 92% compared with 78% in the 40 stage II patients (P = .04). Significant differences in FFTF were not seen by histology (P = .26) or by European Organization for Research and Treatment of Cancer H-5F eligibility (P = .25). CONCLUSION: Mantle irradiation alone in selected patients with early-stage Hodgkin’s disease is associated with disease control rates comparable to those seen with extended field irradiation. The FFTF is especially favorable among stage I patients.

Sign in / Sign up

Export Citation Format

Share Document