scholarly journals Short Androgen Suppression and Radiation Dose Escalation in Prostate Cancer: 12-Year Results of EORTC Trial 22991 in Patients With Localized Intermediate-Risk Disease

2021 ◽  
pp. JCO.21.00855
Author(s):  
Michel Bolla ◽  
Anouk Neven ◽  
Philippe Maingon ◽  
Christian Carrie ◽  
Ana Boladeras ◽  
...  
Keyword(s):  
Prostatic Carcinoma ◽  
Statistical Significance ◽  
External Beam Radiotherapy ◽  
Specific Antigen ◽  
Disease Free Survival ◽  
Long Term Results ◽  
Intermediate Risk ◽  
Free Survival ◽  
Intention To Treat ◽  
Androgen Suppression

PURPOSE The European Organisation for Research and Treatment of Cancer (EORTC) trial 22991 ( NCT00021450 ) showed that 6 months of concomitant and adjuvant androgen suppression (AS) improves event- (EFS, Phoenix) and clinical disease-free survival (DFS) of intermediate- and high-risk localized prostatic carcinoma, treated by external-beam radiotherapy (EBRT) at 70-78 Gy. We report the long-term results in intermediate-risk patients treated with 74 or 78 Gy EBRT, as per current guidelines. PATIENT AND METHODS Of 819 patients randomly assigned between EBRT or EBRT plus AS started on day 1 of EBRT, 481 entered with intermediate risk (International Union Against Cancer TNM 1997 cT1b-c or T2a with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≤ 7 and PSA ≤ 20 ng/mL, N0M0) and had EBRT planned at 74 (342 patients, 71.1%) or 78 Gy (139 patients, 28.9%). We report the trial primary end point EFS, DFS, distant metastasis–free survival (DMFS), and overall survival (OS) by intention-to-treat stratified by EBRT dose at two-sided α = 5%. RESULTS At a median follow-up of 12.2 years, 92 of 245 patients and 132 of 236 had EFS events in the EBRT plus AS and EBRT arm, respectively, mostly PSA relapse (48.7%) or death (45.1%). EBRT plus AS improved EFS and DFS (hazard ratio [HR] = 0.53; CI, 0.41 to 0.70; P < .001 and HR = 0.67; CI, 0.49 to 0.90; P = .008). At 10 years, DMFS was 79.3% (CI, 73.4 to 84.0) with EBRT plus AS and 72.7% (CI, 66.2 to 78.2) with EBRT (HR = 0.74; CI, 0.53 to 1.02; P = .065). With 140 deaths (EBRT plus AS: 64; EBRT: 76), 10-year OS was 80.0% (CI, 74.1 to 84.7) with EBRT plus AS and 74.3% (CI, 67.8 to 79.7) with EBRT, but not statistically significantly different (HR = 0.74; CI, 0.53 to 1.04; P = .082). CONCLUSION Six months of concomitant and adjuvant AS statistically significantly improves EFS and DFS in intermediate-risk prostatic carcinoma, treated by irradiation at 74 or 78 Gy. The effects on OS and DMFS did not reach statistical significance.

scholarly journals Induction Chemotherapy Followed by Pleurectomy Decortication and Hyperthermic Intraoperative Chemotherapy (HITHOC) for Early-Stage Epitheliod Malignant Pleural Mesothelioma—A Prospective Report

2021 ◽  
Vol 10 (23) ◽  
pp. 5542
Author(s):  
Stefano Bongiolatti ◽  
Francesca Mazzoni ◽  
Ottavia Salimbene ◽  
Enrico Caliman ◽  
Carlo Ammatuna ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Malignant Pleural Mesothelioma ◽  
Early Stage ◽  
Disease Free Survival ◽  
Stage I ◽  
Long Term Results ◽  
Pleural Mesothelioma ◽  
Free Survival ◽  
Therapy Regimen ◽  
Platinum Based Chemotherapy

Malignant pleural mesothelioma (MPM) is an aggressive disease with poor prognosis and the current treatment for early-stage MPM is based on a multimodality therapy regimen involving platinum-based chemotherapy preceding or following surgery. To enhance the cytoreductive role of surgery, some peri- or intra-operative intracavitary treatments have been developed, such as hyperthermic chemotherapy, but long-term results are weak. The aim of this study was to report the post-operative results and mid-term outcomes of our multimodal intention-to-treat pathway, including induction chemotherapy, followed by surgery and Hyperthermic Intraoperative THOracic Chemotherapy (HITHOC) in the treatment of early-stage epithelioid MPM. Since 2017, stage I or II epithelioid MPM patients have been inserted in a surgery-based multimodal approach comprising platinum-based induction chemotherapy, followed by pleurectomy and decortication (P/D) and HITHOC with cisplatin. The Kaplan–Meier method was used to estimate overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). During the study period, n = 65 patients affected by MPM were evaluated by our institutional Multidisciplinary Tumour Board; n = 12 patients with stage I-II who had no progression after induction chemotherapy underwent P/D and HITHOC. Post-operative mortality was 0, and complications developed in n = 7 (58.3%) patients. The median estimated OS was 31 months with a 1-year and 3-year OS of 100% and 55%, respectively. The median PFS was 26 months with 92% of a 1-year PFS, whereas DFS was 19 months with a 1-year DFS rate of 83%. The multimodal treatment of early-stage epithelioid MPM, including induction chemotherapy followed by P/D and HITHOC, was well tolerated and feasible with promising mid-term oncological results.

scholarly journals Effect of Chemotherapy With Docetaxel With Androgen Suppression and Radiotherapy for Localized High-Risk Prostate Cancer: The Randomized Phase III NRG Oncology RTOG 0521 Trial

2019 ◽  
Vol 37 (14) ◽  
pp. 1159-1168 ◽  
Author(s):  
Seth A. Rosenthal ◽  
Chen Hu ◽  
Oliver Sartor ◽  
Leonard G. Gomella ◽  
Mahul B. Amin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Distant Metastasis ◽  
Disease Free Survival ◽  
Free Survival ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Androgen Suppression ◽  
Disease Free

PURPOSE Radiotherapy (RT) plus long-term androgen suppression (AS) are a standard treatment option for patients with high-risk localized prostate cancer. We hypothesized that docetaxel chemotherapy (CT) could improve overall survival (OS) and clinical outcomes among patients with high-risk prostate cancer. PATIENTS AND METHODS The multicenter randomized NRG Oncology RTOG 0521 study enrolled patients with high-risk nonmetastatic disease between 2005 and 2009. Patients were randomly assigned to receive standard long-term AS plus RT with or without adjuvant CT. RESULTS A total of 612 patients were enrolled; 563 were evaluable. Median prostate-specific antigen was 15.1 ng/mL; 53% had a Gleason score 9 to 10 cancer; 27% had cT3 to cT4 disease. Median follow-up was 5.7 years. Treatment was well tolerated in both arms. Four-year OS rate was 89% (95% CI, 84% to 92%) for AS + RT and 93% (95% CI, 90% to 96%) for AS + RT + CT (hazard ratio [HR], 0.69; 90% CI, 0.49 to 0.97; one-sided P = .034). There were 59 deaths in the AS + RT arm and 43 in the AS + RT + CT arm, with fewer deaths resulting from prostate cancer in the AS + RT + CT arm versus AS + RT (23 v 16 deaths, respectively). Six-year rate of distant metastasis was 14% for AS + RT and 9.1% for AS + RT + CT, (HR, 0.60; 95% CI, 0.37 to 0.99; two-sided P = .044). Six-year disease-free survival rate was 55% for AS + RT and 65% for AS + RT + CT (HR, 0.76; 95% CI, 0.58 to 0.99; two-sided P = .043). CONCLUSION For patients with high-risk nonmetastatic prostate cancer, CT with docetaxel improved OS from 89% to 93% at 4 years, with improved disease-free survival and reduction in the rate of distant metastasis. The trial suggests that docetaxel CT may be an option to be discussed with selected men with high-risk prostate cancer.

Prostate-specific antigen nadir: the optimum level after irradiation for prostate cancer.

1996 ◽  
Vol 14 (11) ◽  
pp. 2893-2900 ◽  
Author(s):  
F A Critz ◽  
A K Levinson ◽  
W H Williams ◽  
D A Holladay
Keyword(s):  
Prostate Cancer ◽  
Survival Rate ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Disease Free Survival ◽  
External Beam Radiation ◽  
Free Survival ◽  
Psa Nadir ◽  
Disease Free Survival Rate ◽  
Disease Free

PURPOSE The prostate-specific antigen (PSA) nadir that reflects potential cure of prostate cancer by irradiation has not been established. This report attempts to demonstrate the PSA nadir goal for radiotherapy. MATERIALS AND METHODS From January 1984 through April 1994, 536 stage T1T2NO prostate cancer patients were treated with radioactive iodine 125 (125I) prostate implants followed by external-beam radiation. All were staged node-negative: 68% by pelvic node dissection and the remainder by computed tomographic (CT) scan. The mean pretreatment PSA level was 12.4 ng/mL (median, 8.4 ng/mL; range, 0.3 to 188 ng/mL). The median follow-up duration is 40 months (range, 12 to 138). An increasing posttreatment PSA level defined recurrence. RESULTS Patients who achieved a PSA nadir < or = 0.5 ng/mL had a 95% (+/- 4%) 5-year and an 84% (+/- 12%) 10-year disease-free survival rate, compared with a 5-year disease-free survival rate of 29% (+/- 30%) for those who reached a nadir of 0.6 to 1.0 ng/mL (P = .0001). All patients with a nadir greater than 1.0 ng/mL ultimately failed. Eighty percent of all 536 patients are projected to achieve a nadir < or = 0.5 ng/mL and 90% of patients who achieve this PSA level do so within 48 months of treatment (median, 18 months). Compared with pretreatment PSA level and histologic grade, the PSA nadir is the most significant factor associated with disease-free survival. CONCLUSION For most patients to be successfully treated for prostate cancer with radiotherapy, at least with this combination technique, the PSA nadir should become undetectable (< or = 0.5 ng/mL), similar to that after radical prostatectomy. A PSA nadir of < or = 0.5 ng/mL after radiotherapy for prostate cancer may be used as a reasonable indicator of 10-year disease-free survival.

Salvage Cryotherapy for Recurrent Prostate Cancer After Radiotherapy: Variables Affecting Patient Outcome

2002 ◽  
Vol 20 (11) ◽  
pp. 2664-2671 ◽  
Author(s):  
Jonathan I. Izawa ◽  
Lydia T. Madsen ◽  
Shellie M. Scott ◽  
Jean-Paul Tran ◽  
Edward J. McGuire ◽  
...  
Keyword(s):  
Gleason Score ◽  
Clinical Stage ◽  
Specific Antigen ◽  
Disease Free Survival ◽  
Free Survival ◽  
Adenocarcinoma Of The Prostate ◽  
Salvage Cryotherapy ◽  
Locally Recurrent

PURPOSE: To determine the long-term disease-specific survival (DSS) and disease-free survival (DFS) rates after salvage cryotherapy for locally recurrent adenocarcinoma of the prostate and to identify pretreatment factors that have an impact on DSS and DFS. PATIENTS AND METHODS: Between July 1992 and January 1995, 131 patients who had received definitive radiation therapy (XRT) underwent salvage cryotherapy for locally recurrent adenocarcinoma of the prostate. Cryotherapy failure was defined as an increasing postcryotherapy prostate-specific antigen (PSA) level of ≥ 2 ng/mL above the postcryotherapy nadir, a positive prostate biopsy, or radiographic evidence of metastatic disease. Clinical variables were studied to determine whether there was an association with the DSS and DFS. RESULTS: The median follow-up was 4.8 years. The 5-year DSS rates were 87% for patients with a precryotherapy Gleason score ≤ 8 and 63% for those with Gleason scores of 9 and 10 (P = .012). The 5-year DFS rates were 57% for patients with a precryotherapy PSA level of ≤ 10 ng/mL and 23% for those with a PSA level greater than 10 ng/mL (P = .0004). The 5-year DSS rates for patients with a pre-XRT clinical stage of T1 to T2 and those with a clinical stage of T3 to T4 were 94% and 72%, respectively (P = .0041). The 5-year DFS rates for these groups were 90% and 69%, respectively (P = .0057). CONCLUSION: Androgen-independent local recurrences, Gleason score, and pre-XRT clinical stage were important factors that had an impact on DSS and DFS. The subset of patients cured by salvage cryotherapy seems to be small, and patient selection is important.

Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31.

1997 ◽  
Vol 15 (3) ◽  
pp. 1013-1021 ◽  
Author(s):  
M V Pilepich ◽  
R Caplan ◽  
R W Byhardt ◽  
C A Lawton ◽  
M J Gallagher ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Radiation Therapy Oncology Group ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Oncology Group ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Carcinoma Of The Prostate ◽  
Androgen Suppression ◽  
Disease Free

PURPOSE Although androgen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate, its potential value as an adjuvant has not been substantiated. MATERIALS AND METHODS In 1987, the Radiation Therapy Oncology Group (RTOG) initiated a randomized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients had been accessioned to the study. Of these, 945 remained analyzable: 477 on the adjuvant arm and 468 on the observation arm. RESULTS Actuarial projections show that at 5 years, 84% of patients on the adjuvant goserelin arm and 71% on the observation arm remain without evidence of local recurrence (P < .0001). The corresponding figures for freedom from distant metastases and disease-free survival are 83% versus 70% (P < .001) and 60% and 44% (P < .0001). If prostate-specific antigen (PSA) level greater than 1.5 ng is included as a failure (after > or = 1 year), the 5-year disease-free survival rate on the adjuvant goserelin arm is 53% versus 20% on the observation arm (P < .0001). The 5-year survival rate (for the entire population) is 75% on the adjuvant arm versus 71% on the observation arm (P = .52). However, in patients with centrally reviewed tumors with a Gleason score of 8 to 10, the difference in actuarial 5-year survival (66% on the adjuvant goserelin arm v 55% on the observation arm) reaches statistical significance (P = .03). CONCLUSION Application of androgen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression. At this point, with a median follow-up time of 4.5 years, a significant improvement in survival has been observed only in patients with centrally reviewed tumors with a Gleason score of 8 to 10.

809 Phase 2 trial of neoadjuvant and adjuvant PD-1 checkpoint blockade in local-regionally advanced, resectable HNSCC indicates pathological response is associated with high disease-free survival

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A859-A860
Author(s):  
Trisha Wise-Draper ◽  
Shuchi Gulati ◽  
Vinita Takiar ◽  
Sarah Palackdharry ◽  
Francis Worden ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Pathological Response ◽  
Intermediate Risk ◽  
Free Survival ◽  
Disease Free

BackgroundPatients with newly diagnosed, resected, head and neck squamous cell carcinoma (HNSCC) with high-risk (positive margins, extracapsular spread [ECE]) or intermediate-risk pathological features have an estimated 1-year disease free survival (DFS) of 65% and 69%, respectively.1 PD-1/PD-L1 immune checkpoint blockade has improved survival of patients with recurrent/metastatic HNSCC, and preclinical models indicate radiation upregulates PD-L1.2 Therefore, we hypothesized that pre and post-operative administration of the PD-1 inhibitor pembrolizumab would improve 1-year DFS for patients with resectable, loco-regionally advanced (clinical T3/4 and/or ≥2 nodal metastases) HNSCC (NCT02641093).MethodsEligible patients received pembrolizumab (200 mg I.V. x 1) 1-3 weeks before resection. Adjuvant pembrolizumab (q3 wks x 6 doses) was administered with weekly cisplatin (40mg/m2 X 6) and radiation (60-66Gy) for those with high-risk features and radiation alone for patients with intermediate-risk features. The primary endpoint was DFS, which was compared by log-rank test to historical controls (RTOG 9501). Evidence of pathological response to neoadjuvant pembrolizumab was evaluated by comparing pre- and post-surgical tumor specimens for treatment effect (TE) defined as tumor necrosis and/or histiocytic inflammation and giant cell reaction to keratinaceous debris. Response was classified as none (NPR, <20%), partial (PPR, ≥20% and <90%) and major (MPR, ≥90%) pathological response. Gene expression analysis in paired tumor specimens was evaluated by Nanostring.ResultsSixty-six of 84 enrolled patients had received adjuvant pembrolizumab and therefore were evaluable for DFS at the time of interim analysis. Patient characteristics included: median age 59 (range of 27 – 76) years; 30% female; 85% oral cavity, 11% larynx, and 2% human papillomavirus negative oropharynx; 85% clinical T3/4 and 68% ≥2N; 41(51%) high-risk (positive margins, 49%; ECE, 80%). At a median follow-up of 16 months, 1-year DFS was 66% (95%CI 0.48-0.84) in the high-risk group (p=1) and 91% (95%CI 0.79-1) in the intermediate-risk group (versus 69% in RTOG 9501, p=0.05) (figure 1). Among 70 patients evaluable for pathological response, TE was scored as NPR in 40, PPR in 27, and MPR in 3 patients. Patients with pathological response that were also evaluable for DFS (PPR + MPR) had significantly improved 1-year DFS when compared with those with NPR (100% versus 57%, p=0.0033; HR = 0.18 [95%CI 0.05-0.64]) (figure 2). PPR/MPR was associated with robust macrophage infiltration via Nanostring.Abstract 809 Figure 1Disease Free Survival by Pathological RiskPatients were stratified by pathological risk and DFS was measuredAbstract 809 Figure 2Disease Free Survival by Pathological ResponsePaired patient tissue was assessed for treatment effect (TE) and patients with greater than or equal to 20% TE were considered to have developed pathological response. Patients were stratified into responders and non-responders and DFS was determined.ConclusionsNeoadjuvant and adjuvant pembrolizumab led to high DFS in intermediate-risk, but not high-risk, resected HNSCC patients. Pathological response to neoadjuvant pembrolizumab was associated with high 1-year DFS.AcknowledgementsWe’d like to acknowledge the UCCC clinical trials office for their hard work on this study as well as our patients. We’d also like to acknowledge Merck & Co, Inc as they partially funded the clinical trial.Trial RegistrationNCT02641093Ethics ApprovalThis study was approved by the University of Cincinnati IRB with approval number 2015-6798ReferencesCooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350(19):1937-1944. doi:10.1056/NEJMoa032646Oweida A, Lennon S, Calame D, et al. Ionizing radiation sensitizes tumors to PD-L1 immune checkpoint blockade in orthotopic murine head and neck squamous cell carcinoma. Oncoimmunology2017;6(10):e1356153. Published 2017 Aug 3. doi:10.1080/2162402X.2017.1356153

Low Platelet Counts at Diagnosis Predict Better Survival for Patients with Intermediate-Risk Acute Myeloid Leukemia

2019 ◽  
Vol 143 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Yimin Zhang ◽  
Haihui Gu ◽  
Qi Chen ◽  
Ying Zhang ◽  
Hui Cheng ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Negative Impact ◽  
Disease Free Survival ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Risk Patients ◽  
Immature Cells ◽  
Acute Myeloid

Background: Aggressive growth of primitive and immature cells in the bone marrow results in reductions in megakaryocyte and platelet (PLT) counts, leading to thrombocytopenia in acute myeloid leukemia (AML). However, not all AML patients show thrombocytopenia at the time of diagnosis, and the association of PLT count with patient survival is largely unknown. Methods: A retrospective study was performed to determine PLT counts at diagnosis in the peripheral blood in 291 newly diagnosed AML patients and assess the association of PLT counts with the overall survival (OS) and disease-free survival (DFS) of these patients. Results: Low PLT counts (≤40 × 109/L) were associated with better outcomes for the whole cohort (5-year OS, 55.1 ± 3.8 vs. 35.3 ± 3.5%, p < 0.001; 5-year DFS, 49.1 ± 3.8 vs. 25.7 ± 4.0%, p < 0.001) and intermediate-risk patients (5-year OS, 64.5 ± 5.4 vs. 41.0 ± 4.8%, p < 0.001; 5-year DFS, 60.8 ± 5.6 vs. 28.6 ± 5.6%, p < 0.001). Moreover, low PLT counts were related to deeper molecular remission. Low PLT counts correlated with better survival of intermediate-risk AML patients treated with chemotherapy only. Allogeneic hematopoietic stem cell transplantation attenuated the negative impact of high PLT counts on the survival of intermediate-risk patients. Furthermore, univariate and multivariate analyses demonstrated that PLT count at diagnosis was an independent prognostic factor for intermediate-risk AML. Conclusion: PLT count at diagnosis predicts survival for patients with intermediate-risk AML.

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