Adjuvant therapy with gemcitabine and stereotactic body radiation therapy versus gemcitabine alone for resected stage II pancreatic cancer: A prospective, randomized, open label, single-center trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15765-e15765
Author(s):  
Tao Ma ◽  
Xueli Bai ◽  
Qichun Wei ◽  
Shunliang Gao ◽  
Bingfeng Huang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Adjuvant Chemotherapy ◽  
Stereotactic Body Radiation Therapy ◽  
Stage Ii ◽  
Recurrence Free Survival ◽  
Single Center ◽  
Free Survival ◽  
Local Disease Control ◽  
Resected Stage

e15765 Background: Although adjuvant chemotherapy with gemcitabine has for years been the standard of care for resected pancreatic cancer, the role of adjuvant radiation is still debatable. We aimed to investigate the efficacy of gemcitabine combined with stereotactic body radiation therapy (SBRT) as adjuvant therapy for resected stage II pancreatic cancer. Methods: This single center randomized controlled trial was designed to enroll 512 patients with stage II pancreatic cancer that underwent curative-intended radical resection from a large-volume tertiary pancreatic center in China. Patients were randomly assigned to gemcitabine-alone adjuvant chemotherapy or adjuvant SBRT (25 Gray in 5 fractions) followed by gemcitabine chemotherapy. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included locoregional recurrence-free survival (LRFS), overall survival (OS), and incidence of adverse events. Interim analysis was planned at the time of 2.5-years’ enrollment. Results: 40 patients were randomly assigned to treatment between Sep 1, 2015, and Mar 31, 2018 (21 to the gemcitabine group and 19 to the gemcitabine plus SBRT group). Of these, one was excluded because of ineligibility and one did not receive any treatment. The median RFS was 12.4 (9.3-15.6) months in the gemcitabine group and 14.7 (9.2-20.1) months in the gemcitabine plus SBRT group ( P= 0.753), with median LRFS of 18.2 (14.6-21.7) months in the gemcitabine group and 13.1 (9.1-16.8) months in the gemcitabine plus SBRT group ( P= 0.333). The median OS was 21.7 (19.5-24.0) months in the gemcitabine group and 16.9 (12.8-20.9) in the gemcitabine plus SBRT group ( P= 0.066). Grade 3 or 4 neutropenia, thrombocytopenia, nausea or vomiting, and liver dysfunction were all comparable between the two groups. Evaluation of data from the first 40 enrolled patients indicated that the addition of adjuvant SBRT was not associated with either better local disease control or recurrence free survival. And because of failure to achieve the accrual target, the trial was terminated prematurely. Conclusions: Adjuvant SBRT neither provided a survival benefit nor improved local disease control in resected stage II pancreatic cancer. Clinical trial information: NCT02461836.

scholarly journals Upfront Chemotherapy Followed by Stereotactic Body Radiation Therapy with or without Surgery in Older Patients with Localized Pancreatic Cancer: A Single Institution Experience and Review of the Literature

2022 ◽  
Vol 29 (1) ◽  
pp. 308-320
Author(s):  
Abhinav V. Reddy ◽  
Shuchi Sehgal ◽  
Colin S. Hill ◽  
Lei Zheng ◽  
Jin He ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Clinical Outcomes ◽  
Older Patients ◽  
Stereotactic Body Radiation Therapy ◽  
Progression Free Survival ◽  
Radiation Toxicity ◽  
Free Survival ◽  
Stereotactic Body Radiation ◽  
Resection Status

Objective: To report on clinical outcomes and toxicity in older (age ≥ 70 years) patients with localized pancreatic cancer treated with upfront chemotherapy followed by stereotactic body radiation therapy (SBRT) with or without surgery. Methods: Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and toxicity. Results: A total of 57 older patients were included in the study. Median OS was 19.6 months, with six-month, one-year, and two-year OS rates of 83.4, 66.5, and 42.4%. On MVA, resection status (HR: 0.30, 95% CI 0.12–0.91, p = 0.031) was associated with OS. Patients with surgically resected tumors had improved median OS (29.1 vs. 7.0 months, p < 0.001). On MVA, resection status (HR: 0.40, 95% CI 0.17–0.93, p = 0.034) was also associated with PFS. Patients with surgically resected tumors had improved median PFS (12.9 vs. 1.6 months, p < 0.001). There were 3/57 cases (5.3%) of late grade 3 radiation toxicity and 2/38 cases (5.3%) of Clavien-Dindo grade 3b toxicity in those who underwent resection. Conclusion: Multimodality therapy involving SBRT is safe and feasible in older patients with localized pancreatic cancer. Surgical resection was associated with improved clinical outcomes. As such, older patients who complete chemotherapy should not be excluded from aggressive local therapy when possible.

scholarly journals Stereotactic body radiation therapy for early-stage non–small-cell lung cancer in octogenarians and older: an alternative treatment

2020 ◽  
Vol 61 (4) ◽  
pp. 586-593
Author(s):  
Yanping Bei ◽  
Naoya Murakami ◽  
Yuko Nakayama ◽  
Kae Okuma ◽  
Tairo Kashihara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
Early Stage ◽  
Small Cell ◽  
Recurrence Free Survival ◽  
Small Cell Lung ◽  
Free Survival ◽  
Early Stage Nsclc ◽  
Lung Sbrt

ABSTRACT Surgery is the standard modality for early-stage I–II non-small-cell lung cancer (NSCLC). Generally, patients who are &gt;80 years old tend to have more comorbidities and inferior physical status than younger patients. Stereotactic body radiation therapy (SBRT) may provide an alternative treatment for this group of patients. Here, we report our experience using SBRT to in the management of early-stage NSCLC in patients &gt;80 years old. Patients aged ≥80 years old who were diagnosed with early-stage NSCLC and treated with definitive lung SBRT from January 2000 to January 2018 were retrospectively analysed. Local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), cancer-specific survival (CSS), progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were analysed for patients &gt;80 years old. A total of 153 patients were included, with a median age of 85 years (range, 80–94). The median follow-up period and OS was 39.8 months (range, 10–101 months) and 76 months, respectively. The 3-year OS, PFS, CSS, RRFS and LRFS were 65.3, 58.0, 75.7, 73.9 and 85.3%, respectively. Radiation pneumonitis grade 0–1, grade 2, grade 3 and grade 4 was observed in 135 (88.2%), 13 (8.5%), 4 (2.61%) and 1 (0.6%) patient(s), respectively. On multivariate analyses, tumor size, pretreatment C-reactive protein (CRP) value, histology and pretreatment physical state were significantly associated with OS. Definitive lung SBRT appears to have high LRFS and OS without causing high-grade radiation-related toxicities in early-stage NSCLC patients who were &gt;80 years old.

Long-term outcomes with neoadjuvant chemotherapy with or without stereotactic body radiation therapy in patients with borderline resectable and locally advanced pancreatic adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 443-443
Author(s):  
Colin Hill ◽  
Lauren M. Rosati ◽  
Chen Hu ◽  
Wei Fu ◽  
Shuchi Sehgal ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
Locally Advanced ◽  
Survival Outcomes ◽  
Long Term Outcomes ◽  
Free Survival ◽  
Significant Difference ◽  
Multi Agent

443 Background: Patients (pts) withborderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) are at high risk of margin positive resection with upfront surgery. Pre-operative stereotactic body radiation therapy (SBRT) may help sterilize vascular margins, but its additive benefit beyond multi-agent chemotherapy (CTX) is unclear. We report on long-term outcomes from a high-volume institution of BRPC/LAPC pts who were reviewed by a multidisciplinary team and explored after either multi-agent CTX alone or multi-agent CTX followed by SBRT. Methods: Consecutive BRPC/LAPC pts diagnosed 2011-2016 who underwent resection following CTX alone or CTX followed by 5-fraction SBRT (CTX-SBRT) were retrospectively reviewed. Baseline demographic, clinical, and treatment factors were compared between cohorts, and survival analysis was conducted to compare pathologic and survival outcomes. Results: Of 199 pts, 77 received CTX alone and 122 received CTX-SBRT. There was no significant difference between cohorts in age, gender, performance status, tumor location, CA19-9 at diagnosis, or post-CTX CA19-9 values (all p > 0.05). The CTX-SBRT cohort had a higher proportion of pts with LAPC as compared to the CTX cohort (53% vs 22%, p< 0.001). Modified FOLFIRINOX (mFFX) was administered to 55% of pts, while 70% of pts received either mFFX or gemcitabine/abraxane, with no difference between cohorts. Duration of CTX was longer in the CTX-SBRT cohort as compared to the CTX cohort (median 4.6 vs. 2.9 mos, p= 0.03), but adjuvant CTX was not given as often in the CTX-SBRT arm (60.4% vs. 86.4%, p= < 0.001). Notably, 30% of the CTX cohort also received adjuvant chemoradiation. Pathologic response was significantly improved in the CTX-SBRT cohort vs the CTX cohort, specifically negative margins (92% vs 70%, p< 0.001), node negative (59% vs. 42%, p< 0.001), and pathologic complete response (7% vs. 0%, p= 0.02). On multivariable analysis, after controlling for prognostic factors, CTX-SBRT remained significantly associated with margin negative resection ( p< 0.001). Despite having more advanced stage and less adjuvant therapy administration in the CTX-SBRT cohort, there was no significant difference in overall survival after surgery (median OS: 24.6 vs. 22.2 mo, p= 0.79), local progression free survival (14.0 vs. 13.6 mo, p= 0.33), or distant metastasis free survival (16.4 vs. 11.8 mo, p= 0.33). Conclusions: Despite more advanced disease at presentation, BRPC/LAPC pts treated with CTX-SBRT were more likely to undergo margin negative resection and experienced similar survival outcomes, as compared to CTX alone. More data are needed to refine which patients benefit from neoadjuvant SBRT and how RT administration can be optimized to impact survival outcomes.

Pembrolizumab versus placebo as adjuvant therapy in resected high-risk stage II melanoma: Phase 3 KEYNOTE-716 study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS9596-TPS9596 ◽  
Author(s):  
Matteo S. Carlino ◽  
Paolo Antonio Ascierto ◽  
Alexander M. Eggermont ◽  
Jeffrey E. Gershenwald ◽  
Jean Jacques Grob ◽  
...  
Keyword(s):  
High Risk ◽  
Adverse Events ◽  
Distant Metastasis ◽  
Tumor Imaging ◽  
Stage Ii ◽  
Recurrence Free Survival ◽  
Phase 3 ◽  
Double Blind ◽  
Free Survival ◽  
Resected Stage

TPS9596 Background: Adjuvant pembrolizumab showed significantly longer recurrence-free survival than placebo in patients with resected stage III melanoma in the KEYNOTE-054 study. KEYNOTE-716 (NCT03553836) is a randomized, placebo-controlled, double-blind, multicenter phase 3 study of adjuvant pembrolizumab in patients with surgically resected high-risk stage II melanoma. Methods: Key eligibility criteria are age ≥12 y with newly diagnosed, completely resected stage IIB/IIC cutaneous melanoma, defined by the AJCC Cancer Staging Manual, 8th edition (wide excision and negative sentinel lymph node biopsy with no evidence of distant metastasis). Patients with mucosal or uveal melanoma or prior treatment (including radiation) for melanoma beyond resection of primary disease within 12 wk of the start of study treatment were excluded. In this 2-part study, in the double-blind phase (part 1), patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg for patients ≥18 y or 2 mg/kg for patients ≥12 y to < 18 y (maximum dose, 200 mg) or placebo every 3 wk for 17 cycles. Study treatment will begin within 12 wk of complete resection. Tumor imaging will be performed every 24 wk while treatment is ongoing, at the end of treatment, every 6 mo for the first 3 y off treatment, and then yearly for up to 2 y or until recurrence (up to 5 y of total imaging). Adverse events will be recorded until 30 d after treatment end (90 d for serious AEs) and graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the unblinded phase (part 2), patients with confirmed recurrence may be rechallenged (patients received pembrolizumab in part 1) or crossed over to pembrolizumab (patients received placebo in part 1). Resected local or distant recurrence or unresectable disease will be treated for an additional 17 or 35 cycles, respectively. Tumor imaging in part 2 will occur every 12 wk during treatment. The primary end point is recurrence-free survival; secondary end points are distant metastasis-free survival, overall survival, and safety. Approximately 954 patients will be enrolled. Clinical trial information: NCT03553836.

Phase III KEYNOTE-716 study: Adjuvant therapy with pembrolizumab versus placebo in resected high-risk stage II melanoma.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. TPS145-TPS145
Author(s):  
Jason J. Luke ◽  
Paolo Antonio Ascierto ◽  
Matteo S. Carlino ◽  
Alexander M. M. Eggermont ◽  
Jean-Jacques Grob ◽  
...  
Keyword(s):  
High Risk ◽  
Adverse Events ◽  
Distant Metastasis ◽  
Tumor Imaging ◽  
Stage Ii ◽  
Phase Iii ◽  
Recurrence Free Survival ◽  
Double Blind ◽  
Free Survival ◽  
Resected Stage

TPS145 Background: Adjuvant pembrolizumab showed significantly longer recurrence-free survival compared with placebo in resected stage III melanoma in the KEYNOTE-054 study [1]. KEYNOTE-716 is a randomized, placebo-controlled, multicenter phase 3 study of adjuvant pembrolizumab in patients with surgically resected high-risk stage II melanoma. Methods: Patients must be ≥12 years of age and have newly diagnosed, completely resected stage IIB/IIC cutaneous melanoma, defined by the AJCC Cancer Staging Manual, 8th edition [2] (wide excision and negative sentinel lymph node biopsy, with no evidence of distant metastasis). Patients cannot have mucosal or uveal melanoma or have received prior treatment for melanoma, including radiation, beyond resection of primary disease within 12 weeks of the start of study therapy. The study has a 2-part design. In the double-blind phase (part 1), patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg for patients ≥18 years or 2 mg/kg for patients 12-17 years (maximum dose, 200 mg) or placebo every 3 weeks for 17 cycles. Stratification: 1 stratum for pediatric patients (12-17 years); 3 strata for adult patients per T stage (T3b/T4a/T4b). Study treatment will begin within 12 weeks of complete resection. Tumor imaging will be performed every 24 weeks while treatment is ongoing, at the end of treatment, every 6 months for the first 3 years off treatment, and then yearly for up to 2 years or until recurrence (up to 5 years of total imaging). Adverse events will be graded per NCI Common Terminology Criteria for Adverse Events, version 4.0. In the unblinded phase (part 2), patients with confirmed recurrence may be rechallenged (patients received pembrolizumab in part 1) or crossed over to pembrolizumab (patients received placebo in part 1). Resected local or distant recurrence or unresectable disease will be treated for an additional 17 or 35 cycles, respectively. Tumor imaging in part 2 will occur every 12 weeks while treatment is ongoing. The primary end point is recurrence-free survival; secondary end points are distant metastasis-free survival, overall survival, and safety. Approximately 954 patients will be enrolled. Clinical trial information: NCT03553836.

scholarly journals Association of Mixed Lineage Kinase Domain-Like Protein Expression With Prognosis in Patients With Colon Cancer

2016 ◽  
Vol 16 (4) ◽  
pp. 428-434 ◽  
Author(s):  
Xian Li ◽  
Jing Guo ◽  
Ai-Ping Ding ◽  
Wei-Wei Qi ◽  
Pei-Hua Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Protein Expression ◽  
Kinase Domain ◽  
Stage Ii ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Mixed Lineage Kinase ◽  
Low Expression

Background: The mixed lineage kinase domain-like protein has recently been identified as a key downstream component of tumor necrosis factor–induced necroptosis, which is an important pathway of cancer cell death. The goal of the current study is to explore the expression of mixed lineage kinase domain-like protein in colon cancer tissues and evaluate the prognostic value in patients with colon cancer. Methods: We collected normal and cancer colon tissues from 135 patients diagnosed with colon cancer after radical operation during July 2007 to April 2009 at The Affiliated Hospital of Qingdao University. Immunohistochemistry analysis was scored using an established scoring system. Kaplan-Meier survival curves were generated for recurrence-free survival and overall survival for all patients and 2 subsets of patients. The relationship between mixed lineage kinase domain-like protein expression and prognosis parameter (recurrence-free survival, overall survival) was analyzed by univariate and multivariate Cox regression analyses. Results: The median age of all patients was 67 years and 56.3% were male. Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival (78.6 vs 81.2 months; P = .011) in all patients. In the subset of 79 patients who received adjuvant chemotherapy, low expression of mixed lineage kinase domain-like protein was associated with decreased recurrence-free survival (60.4 vs 72.8 months; P = .032) and decreased overall survival (66.3 vs 72.9 months; P = .005). Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival (74.9 vs 79.8 months; P = .006) and recurrence-free survival (69.6 vs 78.8 months; P = .005) among patients with Tumor Node Metastasis (TNM) stage II colon cancer. Conclusions: Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival in all patient-group with resected colon cancer. It is associated with decreased recurrence-free survival and overall survival in the subset of patients who receive adjuvant chemotherapy and patients who were TNM stage II. Mixed lineage kinase domain-like protein may provide important prognostic information in patients with colon cancer.

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