Phase I study of concurrent high-dose three-dimensional conformal radiotherapy (3D-CRT) without elective nodal irradiation with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7546-7546
Author(s):  
I. Sekine ◽  
M. Sumi ◽  
Y. Ito ◽  
H. Nokihara ◽  
N. Yamamoto ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
Optimal Dose ◽  
Stage Iii ◽  
High Dose ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Three Dimensional Conformal Radiotherapy ◽  
3D Crt

7546 Background: The optimal dose of radiotherapy remains unclear in concurrent chemoradiotherapy for unresectable stage III NSCLC. Methods: Eligible patients (unresectable stage III NSCLC, age ≥ 20 years, PS 0–1, V20 ≤ 30%) received cisplatin (80mg/m2 day 1) and vinorelbine (20mg/m2 days 1 and 8) repeated every 4 weeks for 3–4 cycles. The dose of 3D-CRT was 66 Gy in 33 fractions, 72 Gy in 36 fractions, and 78 Gy in 39 fractions at levels 1–3, respectively. The dose-limiting toxicity (DLT), defined as grade ≥3 esophagitis, pneumonitis, myelitis, dermatitis and heart injury, and early stop of protocol treatment, was evaluated in 6–12 patients at each level. Results: Of the 17, 16 and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled into levels 1–3, respectively, of the study. A total of 26 patients were excluded because of V20 > 30% (n=10), overdose to the esophagus (n=8) and brachial plexus (n=2), comorbidity (n=3), or patient refusal (n=3). There were 26 men and 5 women with a median (range) age of 60 (41–75) years. Of these, 23 (74%) had adenocarcinoma and 20 (65%) had stage IIIA disease. The full planned dose of radiotherapy could be administered in all the patients, and more than 80% of the patients received 3–4 cycles of chemotherapy. Grade 3–4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, grade 3 esophagitis and grade 3 pulmonary toxicity were noted in one, two and one patients, respectively. DLT was noted in 17% of the patients at each level. Two (6%) complete and 27 (87%) partial responses were obtained. In a preliminary survival analysis, the median progression-free and overall survivals were determined to be 15.0 months and 37.6 months, respectively. Conclusions: At the level of 78Gy, only 25% of the patients assessed for eligibility were actually eligible. Toxicity was relatively mild up to 78 Gy in this highly selective patient group. Thus, we determined that the recommended dose of 3D-CRT administered concurrently with cisplatin and vinorelbine chemotherapy was 72Gy. [Table: see text]

Multicenter phase II study of concurrent high-dose (72Gy) three-dimensional conformal radiotherapy (3D-CRT) without elective nodal irradiation with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7070-7070 ◽  
Author(s):  
Hidehito Horinouchi ◽  
Ikuo Sekine ◽  
Minako Sumi ◽  
Miyako Satouchi ◽  
Hiroshi Isobe ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
Optimal Dose ◽  
Distant Recurrence ◽  
Stage Iii ◽  
High Dose ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
3D Crt

7070 Background: The optimal dose of radiotherapy remains unclear in concurrent chemoradiotherapy for unresectable stage III NSCLC. We previously concluded that the recommended dose for further trial was 72Gy in a phase I study (Sekine et al., Int J Radiat Oncol Biol Phys. 953-959, 2012). Methods: Eligible patients (unresectable stage III NSCLC, age between 20 and 74, PS 0-1, V20 ≤ 30%) received cisplatin (80 mg/m2 day 1) and vinorelbine (20 mg/m2 days 1 and 8) repeated every 4 weeks for 3-4 cycles. The 3D-CRT started at the first day of chemotherapy at a total dose of 72 Gy in 36 fractions. The primary endpoint was a 2-year survival rate and the planned sample size was 60 to reject the rate of 45% under the expectation of 65% with a power of 90% and an alpha error of 5%. Results: Thirty-one patients from 4 institutions were enrolled between May 2009 and March 2010. This trial was terminated early due to slow accrual and grade 5 pulmonary toxicities in 2 patients. There were 25 men and 6 women with a median (range) age of 59 (32-72) years. Of these, 23 had adenocarcinoma and 21 had stage IIIA disease. The median (range) V20 value was 20 (9-30). The full planned dose of radiotherapy could be administered in 30 (97%) patients, and 26 (84%) of the patients received 3-4 cycles of chemotherapy. During the chemoradiotherapy, grade 3-4 febrile neutropenia, infection and esophagitis were noted in 5, 4 and 1 of the 31 patients, respectively. After completion of the planned chemoradiotherapy, 5 patients had grade 3 or higher radiation pneumonitis, and 2 (6%) of these patients died at 6.6 and 7.3 months after the treatment started. The overall response rate was 97% (95% confidence interval: 83.3-99.9). Twenty-four patients are alive and thirteen patients experienced recurrence (2 had loco-regional recurrences, 7 had distant recurrence and 4 had mixed recurrence pattern) at a median follow up of 16.4 months. Conclusions: Concurrent high-dose (72Gy) 3D-CRT with chemotherapy using cisplatin and vinorelbine may have a too excessive incidence of pulmonary toxicities to warrant any further evaluation.

Results of a Phase II Study Using Estramustine Phosphate and Vinblastine in Combination With High-Dose Three-Dimensional Conformal Radiotherapy for Patients With Locally Advanced Prostate Cancer

2000 ◽  
Vol 18 (9) ◽  
pp. 1936-1941 ◽  
Author(s):  
Michael J. Zelefsky ◽  
William K. Kelly ◽  
Howard I. Scher ◽  
Henry Lee ◽  
Tracy Smart ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
High Dose ◽  
Estramustine Phosphate ◽  
Risk Prostate Cancer ◽  
Grade 3 ◽  
Three Dimensional Conformal Radiotherapy ◽  
3D Crt

PURPOSE: To assess the feasibility and tolerance of neoadjuvant and concomitant estramustine phosphate and vinblastine (EV) with high-dose three-dimensional conformal radiotherapy (3D-CRT) for patients with unfavorable-risk prostate cancer. PATIENTS AND METHODS: Twenty-seven patients with unfavorable-risk prostate cancer were enrolled onto a prospective study to determine the feasibility of combining EV with 3D-CRT. Patients were eligible if any of the following requirements were satisfied: (1) Gleason score ≥ 8 and prostate-specific antigen (PSA) > 10 ng/mL; (2) Gleason score of 7 and PSA > 20 ng/mL; (3) clinical stage T3N0M0 disease with PSA > 20 ng/mL; (4) any patient with T4N0M0 disease; or (5) patients with TXN1MO disease. Therapy consisted of three 8-week cycles of EV and 8 weeks of 3D-CRT. Estramustine phosphate was given orally beginning on week 1 and continued until the completion of 3D-CRT. Each 8-week cycle of vinblastine consisted of 6 weekly intravenous injections followed by a 2-week rest period. Radiation therapy was administered using a three-dimensional conformal approach to a prescription dose of 75.6 Gy. The median follow-up was 26 months (range, 6 to 40 months). RESULTS: Twenty-three (85%) of 27 patients completed the entire course of therapy and were assessable for toxicities and biochemical outcome. Two patients (7%) developed grade 3 hematologic toxicity that resolved, and two patients (7%) developed grade 3 hepatoxicity, manifesting as persistent elevation of serum transaminase levels, necessitating discontinuation of the chemotherapy and withdrawal from the treatment program. The most prominent adverse effects from this regimen were mild to moderate (grade 1 to 2) nausea and fatigue related to estramustine. Mild peripheral edema was seen in 15% of patients and was treated with diuresis. 3D-CRT was tolerated well in these patients. Medications were required for relief of acute grade 2 rectal (gastrointestinal [GI]) and urinary (genitourinary [GU]) symptoms in 35% and 48% of patients, respectively. Three patients developed acute grade 3 GU toxicities. The 2-year actuarial likelihood of late grade 2 GI toxicity was 20%. No late grade 3 or 4 GI toxicities were observed. The 2-year actuarial likelihoods of late grade 2 and 3 GU toxicities were 25% and 12%, respectively. No grade 4 GU toxicity was observed. CONCLUSION: Neoadjuvant and concomitant EV with high-dose 3D-CRT is well tolerated in patients with unfavorable-risk prostate cancer. Although the incidence of modest (grade 2) late GI and GU toxicities seem to be increased compared with 3D-CRT alone or in combination with androgen ablation therapy, no severe toxicities were encountered with this regimen.

Non-pneumonitis immune-mediated adverse events (imAEs) with durvalumab in patients with unresectable stage III NSCLC (PACIFIC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9048-9048
Author(s):  
Jarushka Naidoo ◽  
Johan F. Vansteenkiste ◽  
Corinne Faivre-Finn ◽  
Mustafa Özgüroğlu ◽  
Shuji Murakami ◽  
...  
Keyword(s):  
Stage Iii ◽  
Smoking History ◽  
High Dose ◽  
Thyroid Disorders ◽  
Double Blind ◽  
Unresectable Stage ◽  
Baseline Factors ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Time To Onset

9048 Background: The phase 3 PACIFIC trial established durvalumab (durva) after chemoradiotherapy (CRT) as SoC for pts with unresectable stage III NSCLC. We report exploratory analyses to characterize non-pneumonitis (np) imAEs that occurred with durva in PACIFIC. Methods: PACIFIC was a double blind trial of pts without disease progression after platinum-based concurrent CRT (≥2 cycles). Pts were randomized 2:1 to receive durva 10 mg/kg or placebo (pbo) IV q2w for ≤12 months, stratified by age, sex and smoking history. We characterized the time to onset, duration, and management/outcomes of np imAEs and their association with (1) baseline pt/disease factors and (2) AEs (excluding all-cause pneumonitis). Results: Of 709 treated pts, 19% and 11% experienced imAEs and np imAEs of any grade, respectively; proportionally more had np imAEs with durva (71/475; 15%) vs pbo (5/234; 2%). Thyroid disorders (54/475; 11%), rash/dermatitis (9/475; 2%), and diarrhea/colitis (5/475; 1%) were the most common np imAEs with durva; rash/dermatitis had the shortest time to onset (Table). Among durva treated pts with np imAEs, 11% had grade 3/4 np imAEs, 41% had np imAEs that resolved, and none had fatal np imAEs; interventions included endocrine replacement therapy (73%), systemic corticosteroids (34%), high dose corticosteroids (16%), and discontinuation (10%). There were no apparent differences in baseline factors between pts with or without np imAEs. Durva had a broadly manageable safety profile irrespective of the occurrence of np imAEs. However, a higher proportion of durva treated pts with vs without np imAEs experienced all-cause, grade 3/4 events (41% vs 29%); none were fatal (excl. pneumonitis). Conclusions: Np imAEs occurred infrequently in PACIFIC, but were more common with durva vs pbo; thyroid disorders and rash/dermatitis were the most common np imAEs. Of durva treated pts with np imAEs, 11% experienced np imAEs of grade 3/4. Overall, np imAEs were broadly manageable and did not lead to high rates of discontinuation, and no association with baseline factors was seen, suggesting this should not deter use of durva in eligible pts. Clinical trial information: NCT02125461. [Table: see text]

Predictors of improved outcome for patients with localized prostate cancer treated with neoadjuvant androgen ablation therapy and three-dimensional conformal radiotherapy.

1998 ◽  
Vol 16 (10) ◽  
pp. 3380-3385 ◽  
Author(s):  
M J Zelefsky ◽  
O Lyass ◽  
Z Fuks ◽  
T Wolfe ◽  
C Burman ◽  
...  
Keyword(s):  
Clinical Stage ◽  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
High Dose ◽  
Free Survival ◽  
Androgen Ablation ◽  
Psa Relapse ◽  
Psa Nadir ◽  
Three Dimensional Conformal Radiotherapy ◽  
3D Crt

PURPOSE To identify prognostic variables that predict for improved biochemical and local control outcome in patients with localized prostatic cancer treated with neoadjuvant androgen deprivation (NAAD) and three-dimensional conformal radiotherapy (3D-CRT). MATERIALS AND METHODS Between 1989 and 1995, 213 patients with localized prostate cancer were treated with a 3-month course of NAAD that consisted of leuprolide acetate and flutamide before 3D-CRT. The purpose of NAAD in these patients was to reduce the preradiotherapy target volume so as to decrease the dose delivered to adjacent normal tissues and thereby minimize the risk of morbidity from high-dose radiotherapy. The median pretreatment prostate-specific antigen (PSA) level was 15.3 ng/mL (range, 1 to 560 ng/mL). The median 3D-CRT dose was 75.6 Gy (range, 64.8 to 81 Gy), and the median follow-up time was 3 years (range, 1 to 7 years). RESULTS The significant predictors for improved outcome as identified in a multivariate analysis included pretreatment PSA level < or = 10.0 ng/mL(P < .00), NAAD-induced preradiotherapy PSA nadir < or = 0.5 ng/mL (P < .001), and clinical stage < or = T2c (P < .04). The 5-year PSA relapse-free survival rates were 93%, 60%, and 40% for patients with pretreatment PSA levels < or = 10 ng/mL, 10 to 20 ng/mL, and greater than 20 ng/mL, respectively (P < .001). Patients with preradiotherapy nadir levels < or = 0.5 ng/mL after 3 months of NAAD experienced a 5-year PSA relapse-free survival rate of 74%, as compared with 40% for patients with higher nadir levels (P < .001). The incidence of a positive biopsy among 34 patients pretreated with androgen ablation was 12%, as compared with 39% for 117 patients treated with 3D-CRT alone who underwent a biopsy (P < .001). CONCLUSION For patients treated with NAAD and high-dose 3D-CRT, pretreatment PSA, preradiotherapy PSA nadir response, and clinical stage are important predictors of biochemical outcome. Patients with NAAD-induced PSA nadir levels greater than 0.5 ng/mL before radiotherapy are more likely to develop biochemical failure and may benefit from more aggressive therapies.

scholarly journals Radiotherapy for Adult Medulloblastoma: Evaluation of Helical Tomotherapy, Volumetric Intensity Modulated Arc Therapy, and Three-Dimensional Conformal Radiotherapy and the Results of Helical Tomotherapy Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Sun Zong-wen ◽  
Yang Shuang-yan ◽  
Du Feng-lei ◽  
Cheng Xiao-long ◽  
Li Qinglin ◽  
...  
Keyword(s):  
Helical Tomotherapy ◽  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
High Dose ◽  
Female Patients ◽  
Adult Medulloblastoma ◽  
Arc Therapy ◽  
Three Dimensional Conformal Radiotherapy ◽  
Dose Radiation ◽  
3D Crt

Introduction. All adult medulloblastoma (AMB) patients should be treated with craniospinal irradiation (CSI) postoperatively. Because of the long irradiation range, multiple radiation fields must be designed for conventional radiotherapy technology. CSI can be completed in only one session with helical tomotherapy (HT). We evaluated the dose of HT, volumetric intensity modulated arc therapy (VMAT), and three-dimensional conformal radiotherapy (3D-CRT) of AMB and the results of 5 cases of AMB treated with HT. Methods. Complete craniospinal and posterior cranial fossa irradiation with HT, VMAT, and 3D-CRT and dose evaluation were performed. And results of 5 cases of AMB treated with HT were evaluated. Results. A large volume of tissue was exposed to low dose radiation in the organs at risk (OAR), while a small volume was exposed to high dose radiation with HT. The conformity and uniformity of the targets were good with HT and VMAT, and the volume of targets exposed to high dose with VMAT was larger than that of HT. The uniformity of 3D-CRT was also good, but the dose conformity was poor. The main toxicity was hematologic toxicity, without 4th-degree bone marrow suppression. There was 3rd-degree inhibition in the white blood cells, hemoglobin, and platelets. The three female patients suffered menstrual disorders during the course of radiation. Two female patients with heavy menstruation suffered 3rd-degree anemia inhibition, and 2 patients suffered amenorrhea after radiotherapy. Although menstrual cycle was normal, the third patient was not pregnant. Conclusion. CSI with HT is convenient for clinical practice, and the side effects are mild. With good conformity and uniformity, VMAT can also be used for selection in CSI. For poor conformity, 3D-CRT should not be the priority selection for CSI. In female patients, the ovaries should be protected.

Three-Dimensional Conformal Radiotherapy, Temozolomide Chemotherapy, and High-Dose Fractionated Stereotactic Boost in a Protocol-Driven, Postoperative Treatment Schedule for High-Grade Gliomas

2009 ◽  
Vol 95 (3) ◽  
pp. 329-337 ◽  
Author(s):  
Luigi Pirtoli ◽  
Giovanni Rubino ◽  
Stefania Marsili ◽  
Giuseppe Oliveri ◽  
Marta Vannini ◽  
...  
Keyword(s):  
Survival Rates ◽  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
Postoperative Treatment ◽  
High Dose ◽  
Treatment Schedule ◽  
Radiotherapy Group ◽  
Three Dimensional Conformal Radiotherapy ◽  
Temozolomide Chemotherapy ◽  
3D Crt

Aims and background No available scientific report deals with high-dose (≥70 Gy) radiotherapy plus temozolomide chemotherapy (TMZ CHT) in high-grade gliomas. The survival results of a protocol-driven, postoperative treatment schedule are reported here to contribute to the discussion on this issue. Methods and study design Uniform criteria were prospectively adopted for case selection during the period 1993–2006 in the management of 123 patients, and we progressively introduced three-dimensional conformal radiotherapy (3D-CRT, 60 Gy), TMZ CHT and a high-dose (70 Gy) stereotactic boost (HDSRT) in the treatment schedule. Palliative radiotherapy was delivered by whole brain irradiation (WBI, 50 Gy) for bulky tumors, whereas radical irradiation was performed with 3D-CRT throughout the study period. Two periods of accrual are considered: 36 patients were treated before 31 December 1999 (29.25%) and 87 (70.75%) after 1 January 2000. This subdivision was due to the implementation of HDSRT hardware and TMZ CHT from January 2000. Results The median overall survival was 13 months and the 1-, 2- and 3-year survival rates were 53%, 19.5% and 11.6%, respectively. The differences in survival related to the treatment variables were highly significant, both in univariate and multivariate analysis. The median survival and 1-, 2- and 3-year survival rates in the palliative WBI group were 9.75 months and 37%, 2%, and 0%, respectively; in the 3D-CRT group 17.25 months and 64%, 34%, and 15%, respectively; in the TMZ CHT concomitant with radiotherapy group 20 months and 61%, 39%, and 21%, respectively; in the TMZ CHT concomitant with and sequential to radiotherapy group 25.75 months and 84%, 54%, and 26%, respectively, and in the HDSRT group 22 months and 72%, 48%, and 37%, respectively. No symptomatic radiation necrosis occurred in any of the groups. Conclusions The results reported here are generally better than those reported in the literature. The selection of patients on the basis of favorable prognostic factors and suitability to the currently available, aggressive postoperative treatment resources can be the mainstay for improving therapeutic results. In particular, the new treatment option reported here (HDSRT in association with TMZ CHT) proved to be safe and effective in obtaining a relatively favorable outcome.

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