High-dose 3D chemoradiotherapy trials in stage III non-small cell lung cancer (NSCLC) at the University of North Carolina: Long-term follow up and late complications

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7145-7145 ◽  
Author(s):  
C. B. Lee ◽  
M. A. Socinski ◽  
L. Lin ◽  
D. T. Moore ◽  
D. E. Morris ◽  
...  

7145 Background: Combined modality treatment is the standard of care for patients (pts.) with unresectable stage III NSCLC. Dose escalation of radiotherapy and the use of concurrent chemotherapy are two strategies attempting to improve survival and locoregional control. The intensification of therapy increases the risk of both early and late treatment related toxicities. Methods: From 5/1996 to 8/2004, 112 stage III NSCLC pts. were entered into 4 Phase I/II trials to assess the safety and feasibility of high-dose (74–90 Gy) thoracic conformal radiotherapy (TCRT) in QD or BID fractions. All pts. were treated with platinum-based induction chemotherapy; 3 of the trials also used concurrent chemotherapy. Results: The median follow up of survivors (29/112) on these trials was 4.9 years. The overall response rate after combined modality therapy was 47% (53/112) (CR 4%, 5/112; PR 43%, 48/112). 27% (30/112) had stable disease. The median survival (with 95% CI) was 24 months (18–31 months). 1-, 3-, and 5-year overall survival was 69% (60–77%), 36% (27–45%), and 24% (16–33%) respectively. Late complications of therapy (defined as >90 days post radiotherapy reported to date) are displayed in the table. Two pts. developed a second primary (1 lung, 1 liver carcinoid). In total, 22% (25/112) had late complications. These patients appear to have a significantly better overall survival (p = .007). 12% (13/112) had a brain-only recurrence, although this did not seem to significantly impact overall survival (p = .82). Conclusions: 1) High-dose TCRT is feasible and results in promising survival outcomes. 2) Late complications occur in a minority of patients suggesting the potential benefit of more aggressive TCRT is not outweighed by its risk. 3) Interestingly, brain-only recurrences did not significantly impact survival in these trials. [Table: see text] [Table: see text]

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5535-5535 ◽  
Author(s):  
Chun-yan Chen ◽  
Chong Zhao ◽  
Li Gao ◽  
Jin-yi Lang ◽  
Jian-ji Pan ◽  
...  

5535 Background: To evaluate the safety and efficacy outcomes of concurrent cetuximab plus IMRT and cisplatin in Chinese patients with LA NPC. Methods: Patients with primary stage III-IVb (UICC/AJCC 2002 staging system) and non-keratinizing NPC were enrolled in this prospective, multicentric, phase II study. Cisplatin (80mg/m2,q3week) and cetuximab (400mg/m2 one w before radiation, and then 250mg/m2/w) were given concurrently. The prescription dose of IMRT to GTVnx (primary tumor in nasopharynx) was 66 Gy - 75.9 Gy, GTVnd (positive cervical lymph nodes) was 60 Gy - 70Gy, The response rate was evaluated according to RECIST 1.0 criteria, and adverse events (AEs) were graded according to NCI CTCAE V3.0 criteria. Results: From July 2008 to April 2009, 100 patients were enrolled (74 male), with median age of 43 years. The proportion of stage III, IVa and IVb patients were 71%, 22% and 7% respectively. 99% of enrolled patients completed the planned treatment. AEs were within the expected range and manageable. No toxic death occurred during the treatment. Acneiform skin eruptions, mucositis, in-field dermatitis, xerostomia and neucopenia were the most common seen AEs, with 64% grade 2/3 acneiform eruptions, 26% grade 2/3 in-field dermatitis, 90% ≥ grade 2 mucositis (2 cases of grade 4 mucositis with spontaneous bleeding), 40% ≥ grade 2 xerostomia and 8% grade 2/3 neucopenia. With a median follow-up time of 23.5 months, the 2 year overall survival (OS), disease-free survival (DFS), local recurrence-free survival, regional (cervical lymph node) recurrence free survival and distant metastasis-free survival rates for the ITT population were 91%, 89%, 90%, 90% and 89%, respectively Multivariate analysis showed that N stage was the only prognostic factor for OS (p=0.0392, HR=2.946) and DFS (p=0.0062, HR=4.246) in these patients. Conclusions: Cetuximab combined with IMRT plus concurrent cisplatin in patients with LA NPC shows satisfactory 2-year locoregional control rate and 2-year overall survival. The combination seems to be well tolerated with a manageable side-effect profile.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19503-19503 ◽  
Author(s):  
S. E. Schild ◽  
S. J. Mandrekar ◽  
A. Jatoi ◽  
W. L. McGinnis ◽  
P. J. Stella ◽  
...  

19503 Background: This study was performed to assess the value of combined modality therapy in elderly patients by comparing the differences in outcome of those who received radiotherapy (RT) alone or RT plus chemotherapy for stage III NSCLC. Methods: North Central Cancer Treatment Group (NCCTG) performed 2 recent phase III trials for stage III NSCLC. The first trial, 90–24–51, included 3 arms: once-daily radiotherapy (QDRT) alone, twice daily RT (BIDRT) alone, and concurrent chemotherapy plus BIDRT. The second trial, 94–24- 52 included 2 arms and compared concurrent chemotherapy with either QDRT or BIDRT. The chemotherapy arms of both trials included etoposide and cisplatin administered concurrently with RT. Only the patients ≥65 years of age (elderly) who participated in these trials were included in this analysis. Results: Of the 166 elderly patients included in this analysis, 37 received RT alone and 129 received concurrent chemotherapy plus RT. The median and 5-year survival rates were 10.5 months and 5.4% for the RT alone group compared to 13.7 months and 14.7% for the RT plus chemotherapy group (log-rank p=0.05). Patients who received RT plus chemotherapy experienced significantly greater severe (grade ≥3) toxicity than those who received RT alone (89.9% versus 32.4%, p < 0.01). Conclusions: Elderly patients who participated in these trials appear to gain a survival advantage from RT and chemotherapy compared to RT alone. As is the case with younger patients, this benefit comes at the cost of additional toxicity. No significant financial relationships to disclose.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7501-7501 ◽  
Author(s):  
Jeffrey D Bradley ◽  
Rebecca Paulus ◽  
Ritsuko Komaki ◽  
Gregory A. Masters ◽  
Kenneth Forster ◽  
...  

7501 Background: The first objective of RTOG 0617 was to compare the overall survival(OS) of patients(pts) treated with standard-dose(SD)(60Gy) versus high-dose(HD)(74Gy) radiotherapy with concurrent chemotherapy(CT). Methods: This Phase III Intergroup trial randomized 464 pts with Stage III NSCLC to the SD(60Gy) vs. HD(74Gy) arms prior to closure of the HD arm. Concurrent CT included weekly paclitaxel(45 mg/m2) and carboplatin(AUC=2). Pts randomized to cetuximab received a 400 mg/m2 loading dose on Day 1 followed by weekly doses of 250 mg/m2. All pts were to receive consolidation CT. We are reporting the final results on radiation dose. Results: 464 pts were accrued prior to closure of the HD arm in 6/11, of which 419 were eligible for analysis. Median follow up was 17.2 months. There were 2 and 10 grade 5 treatment-related adverse events(AEs) on the SD and HD arms, respectively. Grade 3+AEs were 74.2% and 78.2% on SD and HD arms, respectively (p=0.34). The median survival times and 18-month OS rates for the SD and HD arms were 28.7 vs 19.5 months, and 66.9% vs 53.9% respectively (p=0.0007). The primary cause of death was lung cancer (72.2% vs 73.5%)(p=0.84). Local failure rates at 18 months were 25.1% vs 34.3% for SD and HD patients, respectively(p=0.03). Local-regional and distant failures at 18 months were 35.3% vs 44%(p=0.04) and 42.4% vs 47.8%(p=0.16) for SD and HD arms, respectively. Factors predictive of less favorable OS on multivariate analysis were higher radiation dose, higher esophagitis/dysphagia grade, greater gross tumor volume, and heart volume >5 Gy. Conclusions: In this setting of chemoradiation for locally-advanced Stage III NSCLC, 60 Gy is superior to 74 Gy in terms of OS and local-regional control. The effect of the anti-EGFR antibody (cetuximab) awaits further follow up. This project was supported by RTOG grant U10 CA21661, CCOP grant U10 CA37422, and ATC U24 CA 81647 from the National Cancer Institute (NCI) and Eli Lilly and Company. Clinical trial information: NCT00533949.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A304-A304
Author(s):  
Lukas Kaesmann ◽  
Julian Taugner ◽  
Chukwuka Eze ◽  
Claus Belka ◽  
Farkhad Manapov

BackgroundChemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is a new standard of care for inoperable stage III NSCLC. The present study aims to evaluate the oncological outcome of patients treated with CRT alone to those treated with CRT and durvalumab (CRT-IO) in the real-world setting.MethodsRetro- and prospectively collected data of 133 consecutive inoperable stage III NSCLC patients treated between 2011–2019 were evaluated. Local-regional-recurrence-free-survival (LRPFS - defined as progression in the mediastinum, hilum and/or supraclavicular region at both sides and the involved lung), progression-free survival (PFS) and overall survival (OS) were evaluated from last day of thoracic radiotherapy (TRT).ResultsMedian age at diagnosis was 68.5 years; 44 (33%) were female; 58 (44%) were diagnosed with adenocarcinoma. All patients were irradiated to a total dose of at least 60 Gy (EQD2). Median PTV was 709.8 cc (range: 181–1958 cc). 113 (85%) patients were treated with CRT and 20 (15%) PD-L1 expressing patients with CRT-IO. 83% of patients received two cycles of concomitant platinum-based chemotherapy. Median time to initiation of durvalumab after CRT was 0.8 months (range: 0.4–2.1). Median follow-up for entire cohort was 33.3 months (range: 4.8–111.8) and median overall survival (OS) was 24.7 (95% CI: 18.9–30.4) months. In the CRT-IO cohort after a median follow-up of 15.5 (range: 5.1–20.2) months, no deaths were reported at the time of evaluation (August 2020). Improved LRPFS (p=0.013), PFS (p=0.033) and OS (p=0.002) were correlated with CRT-IO compared to the historical cohort of conventional CRT patients.After propensity-score matching (PSM) analysis with age, gender, histology, tumor volume and treatment mode and exact matching for T-and N-stage, 18 CRT-IO patients were matched 1:2 to 36 CRT patients. 12-month LRPFS, PFS and OS rates in the CRT-IO vs CRT cohort were 80% vs 38.8% (p=0.001), 50% vs 22% (p=0.013) and 100% vs 75% (p=0.002), respectively. Also regarding intracranial failure, 6-month brain metastases rates were 0% vs. 6% in the CRT-IO vs CRT cohort (p=0.290).ConclusionsThis real-world analysis demonstrates that durvalumab after CRT has led to significant improvement of local-regional control, PFS and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort.AcknowledgementsThe study was partly presented at 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO).Trial RegistrationN/AEthics ApprovalThe study was approved by Ludwig-Maximilians-University (LMU), Munich, Germany: Institution’s Ethics Board, approval number 17-230.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1613
Author(s):  
Julian Taugner ◽  
Lukas Käsmann ◽  
Chukwuka Eze ◽  
Amanda Tufman ◽  
Niels Reinmuth ◽  
...  

Concurrent chemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is a new standard of care for inoperable stage III NSCLC. The present study compares the oncological outcome of patients treated with CRT to those treated with CRT and durvalumab (CRT-IO) in the real-world setting. The analysis was performed based on the retro- and prospectively collected data of 144 consecutive inoperable stage III NSCLC patients treated between 2011–2020. Local-regional-progression-free-survival (LRPFS—defined as progression in the mediastinum, hilum and/or supraclavicular region at both sites and the involved lung), progression-free survival (PFS), and overall survival (OS) were evaluated from the last day of thoracic radiotherapy (TRT). Median follow-up for the entire cohort was 33.1 months (range: 6.3–111.8) and median overall survival was 27.2 (95% CI: 19.5–34.9) months. In the CRT-IO cohort after a median follow-up of 20.9 (range: 6.3–27.4) months, median PFS was not reached, LRPFS (p = 0.002), PFS (p = 0.018), and OS (p = 0.005) were significantly improved vs. the historical cohort of conventional CRT patients. After propensity-score matching (PSM) analysis with age, gender, histology, tumor volume, and treatment mode, and exact matching for T-and N-stage, 22 CRT-IO patients were matched 1:2 to 44 CRT patients. Twelve-month LRPFS, PFS, and OS rates in the CRT-IO vs. CRT cohort were 78.9 vs. 45.5% (p = 0.002), 60.0 vs. 31.8% (p = 0.007), and 100 vs. 70.5% (p = 0.003), respectively. This real-world analysis demonstrated that durvalumab after CRT led to significant improvement of local-regional control, PFS, and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort.


Author(s):  
Sobin V. Jacob ◽  
Arvind Sathyamurthy ◽  
Jeba Karunya Ramireddy ◽  
Anitha Thomas ◽  
Kaalindi Singh ◽  
...  

Abstract Aim: To analyse the presentation, treatment strategies and outcomes of neuroendocrine carcinoma of cervix treated with multi-modality approach at our institute. Materials and methods: The data of patients diagnosed to have cervical cancer between October 2004 and November 2018 were retrieved, and 14 patients of neuroendocrine carcinoma cervix who received treatment in our institution were identified. The patients were analysed based on demographic characteristics, disease stage, pathological characteristics, treatment and follow-up. The median overall survival and disease-free survival were calculated. Results: Median follow-up period was 8 months (range 1–52 months). Six patients died within 4 months of completion of treatment due to disease progression. Median overall survival was 12 months and median disease-free interval was 5·5 months. Four of the patients who underwent combined modality treatment consisting of neoadjuvant chemotherapy, concurrent chemoradiation therapy and brachytherapy are still on regular follow-up and are disease-free. Conclusion: Neuroendocrine carcinoma of the cervix is a rare but aggressive histological subtype. Combined modality approach with judicious use of systemic chemotherapy along with surgery and radiation therapy is essential for optimal outcomes.


Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6193
Author(s):  
Jian-Yue Jin ◽  
Chen Hu ◽  
Ying Xiao ◽  
Hong Zhang ◽  
Rebecca Paulus ◽  
...  

Background: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: This is a secondary study of a phase III trial, NRG/RTOG 0617, in patients with stage III NSCLC treated with radiation-based treatment. The EDIC was computed as equivalent uniform dose to the entire blood based on radiation doses to all blood-containing organs, with consideration of blood flow and fractionation effect. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and local progression-free survival (LPFS). The EDIC–survival relationship was analyzed with consideration of clinical significant factors. Results: A total of 456 patients were eligible. The median EDIC values were 5.6 Gy (range, 2.1–12.2 Gy) and 6.3 Gy (2.1–11.6 Gy) for the low- and high-dose groups, respectively. The EDIC was significantly associated with OS (hazard ratio [HR] = 1.12, p = 0.005) and LPFS (HR = 1.09, p = 0.02) but PFS (HR = 1.05, p = 0.17) after adjustment for tumor dose, gross tumor volume and other factors. OS decreased with an increasing EDIC in a non-linear pattern: the two-year OS decreased first with a slope of 8%/Gy when the EDIC < 6 Gy, remained relatively unchanged when the EDIC was 6–8 Gy, and followed by a further reduction with a slope of 12%/Gy when the EDIC > 8 Gy. Conclusions: The EDIC is a significant independent risk factor for poor OS and LPFS in RTOG 0617 patients with stage III NSCLC, suggesting that radiation dose to circulating immune cells is critical for tumor control. Organ at risk for the immune system should be considered during RT plan.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 765-765 ◽  
Author(s):  
Andreas Engert ◽  
Peter Borchmann ◽  
Annette Pluetschow ◽  
Bastian von Tresckow ◽  
Jana Markova ◽  
...  

Abstract Abstract 765 Purpose: Combined modality treatment consisting of 4 cycles of chemotherapy and IF-RT is the standard treatment for early unfavorable HL. Overall survival (OS) and freedom from treatment failure (FFTF) at 5 years in this group of patients was 91% and 83%, respectively, in our prior HD8 study. Thus, the rationale for HD14 was to improve on these results by increasing dose intensity using BEACOPP escalated. Methods: Between January 2003 and July 2008, 1655 patients with histologically confirmed diagnosis of Hodgkin lymphoma in early unfavorable stages were randomized. Patients had to be 16–60 years old and have CS I, IIA with one of the following risk factors: large mediastinal mass (a), extranodal disease (b), elevated ESR (c), or ≥ 3 nodal areas (d), IIB with risk factors c or d). Patients were randomized to either 4 cycles of ABVD (arm A) or 2 cycles BEACOPP escalated followed by 2 cycles ABVD (arm B). All patients received 30Gy IF-RT after chemotherapy. Primary objective was the improvement of FFTF. Results: The full analysis set comprised 1623 patients (98.1%) who were documented and followed for treatment effects; 818 were in arm A and 805 in arm B. Patient characteristics were well balanced between the two arms with a median age of 33.6 years and most patients in stage IIA (67%). The overall response rate to treatment was 95% in each arm. With a median follow-up of 42.4 months, 20 patients had died in each arm; 19 patients in arm A had secondary neoplasia compared to 16 patients in arm B. Progressive disease was observed in 2.9% versus 0.9% of patients in arms A and B, respectively; early relapse rates were 2.8% versus 0.9%, and late relapse rates were 2.3% versus 0.9%. The estimated 4-year FFTF rate was 89.3% in arm A and 94.7% in arm B (p=0,0001, hazard ratio HR=2.04, 95%-CI: 1.39–2.94). There was no significant difference in overall survival yet (p=0.95). Acute grade III-IV toxicity rates of chemotherapy were higher in arm B (87.1%) than in arm A (50.7%) with leucopenia rates of 79% versus 24%, hair loss 48% versus 24%, thrombocytopenia 22% versus 0.1% and anemia 9% versus 1% in arms B and A respectively. 7.3% of patients had grade III/IV infections in arm B as compared to 3.4% in arm A. However, we observed no differences in treatment-related death or secondary neoplasia rates between treatment arms. Conclusion: Intensifying treatment for patients with early unfavorable HL using 2 cycles of BEACOPP escalated followed by 2 × ABVD and IFRT results in a significant improvement in tumor control as compared to our prior standard of 4 × ABVD plus IFRT. As defined in the study protocol, this more aggressive treatment was implemented as new standard of care for early unfavorable HL in our follow-up study (GHSG HD17). Disclosures: Greil: Cephalon: Research Funding.


1984 ◽  
Vol 6 (1) ◽  
pp. 10-19
Author(s):  
Giulio J. D'Angio

Major advances have been made in the understanding and management of the malignant diseases of childhood. More than 50% of children with cancer can now be expected to survive five or more years; a few decades ago, most of these patients died within 1 year. These good results have been obtained through the use of combined-modality therapy; that is, the conjoined use of surgery, radiation therapy, and multiple-agent chemotherapy. Wilms' tumor provides a spectacular example (Fig 1). Although achieving higher cure rates, combined-modality treatment is often rigorous, and has its associated early and late complications. The goals of modern pediatric oncology reflect both of these facts. Higher cure rates continue to be sought, but there is a growing recognition that not all patients need maximum treatment. Therapy can now be modulated according to well-defined prognostic factors for most of the malignant conditions. In that way, the most aggressive therapies are reserved for those at highest risk, while those with a good prognosis can be managed less intensively. The objectives of modern management, then, are to cure most patients while at the same time minimizing, as much as possible, the associated deleterious late consequences of successful treatment. wilms' tumor and neuroblastoma serve as good examples to demonstrate the above points.


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