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1.
Int J Radiat Oncol Biol Phys ; 112(1): 146-157, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34400269

ABSTRACT

PURPOSE: A multi-institutional phase 2 trial assessed long-term outcomes of dose-painted intensity modulated radiation therapy (IMRT) with 5-fluorouracil (5FU) and mitomycin-C (MMC) for anal canal cancer. METHODS AND MATERIALS: T2-4N0-3M0 anal cancers received 5FU (1000 mg/m2/d, 96-hour infusion) and MMC (10 mg/m2 bolus) on days 1 and 29 of dose-painted IMRT prescribed as follows: T2N0 = 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes, 28 fractions; T3-4N0-3 = 45Gy elective nodal, 50.4 Gy ≤3 cm and 54 Gy >3cm metastatic nodal and 54 Gy anal tumor planning target volumes, 30 fractions. Local-regional failures, distant metastases, and colostomy failures were assessed using the cumulative incidence method, and disease-free survival, overall survival, and colostomy-free survival were assessed using the Kaplan-Meier method. Late effects were scored using National Cancer Institute-Common Terminology Criteria for Adverse Events v3. RESULTS: Of 52 patients, 54% were stage II, 25% were stage IIIA, and 21% were stage IIIB. Median follow-up was 7.9 years (min-max, 0.02-9.2 years). Local-regional failure, colostomy failures, distant metastases, overall survival, disease-free survival, and colostomy-free survival at 5 years are 16% (95% confidence interval [CI], 7%-27%), 10% (95% CI, 4%-20%), 16% (95% CI, 7%-27%), 76% (95% CI, 61%-86%), 70% (95% CI, 56%-81%), and 74% (95% CI, 59%-84%); and at 8 years they are 16% (95% CI, 7%-27%), 12% (95% CI, 5%-23%), 22% (95% CI, 12%-34%), 68% (95% CI, 53%-79%), 62% (95% CI, 47%-74%) and 66% (95% CI, 51%-77%), respectively. Eight patients experienced local-regional failure, with 5 patients having persistent disease at 12 weeks. No isolated nodal failures occurred in the microscopic elective nodal volumes. Six patients required colostomy-5 for local-regional salvage and 1 for a temporary ostomy for anorectal dysfunction. Rates of late adverse events included: 28 patients (55%) with grade 2, 8 patients (16%) with grade 3, 0 patients with grade 4, and 2 patients (4%) with grade 5 events (sinus bradycardia and myelodysplasia, possibly owing to chemotherapy). Only 11 patients reported grade 1 to 3 sexual dysfunction. CONCLUSIONS: Dose-painted IMRT with 5FU/MMC for the treatment of anal canal cancer yields comparable long-term efficacy as conventional radiation cohorts. Enhanced normal tissue protection lowered rates of grade 3 and higher late effects without compromising pelvic tumor control.


Subject(s)
Anus Neoplasms , Carcinoma, Squamous Cell , Radiotherapy, Intensity-Modulated , Anal Canal , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Anus Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Fluorouracil/adverse effects , Humans , Mitomycin/adverse effects , Morbidity , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods
2.
Int J Radiat Oncol Biol Phys ; 99(2): 417-426, 2017 10 01.
Article in English | MEDLINE | ID: mdl-28871992

ABSTRACT

PURPOSE: To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. METHODS AND MATERIALS: Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. RESULTS: Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). CONCLUSIONS: Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a significant multivariate predictor for improved outcome when including patients treated with NCRT at another institution.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy/methods , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/mortality , Rectal Neoplasms/therapy , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemoradiotherapy/adverse effects , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Kaplan-Meier Estimate , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Matched-Pair Analysis , Middle Aged , Neoadjuvant Therapy/adverse effects , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Preoperative Care , Radiotherapy/methods , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology
3.
Int J Radiat Oncol Biol Phys ; 98(2): 400-408, 2017 06 01.
Article in English | MEDLINE | ID: mdl-28463160

ABSTRACT

PURPOSE: NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). METHODS AND MATERIALS: NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structure receiving doses ≥5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade ≥2 acute and late GI AEs, and grade ≥3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs). RESULTS: Among 52 evaluable patients, grade ≥2 acute, grade ≥2 late, and grade ≥3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P<.05) toward statistically significant associations were observed between grade ≥2 acute GI AEs and small bowel dose (V20-V40), grade ≥2 late GI AEs and APC dose (V60), grade ≥3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size >4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade ≥2 GI AEs. CONCLUSIONS: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies.


Subject(s)
Antineoplastic Agents/adverse effects , Anus Neoplasms/therapy , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/adverse effects , Intestine, Small/radiation effects , Radiotherapy, Intensity-Modulated/adverse effects , Acute Disease , Adult , Age Factors , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Anus Neoplasms/diagnostic imaging , Anus Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy/methods , Colon/diagnostic imaging , Feasibility Studies , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Intestine, Small/diagnostic imaging , Male , Middle Aged , Mitomycin/administration & dosage , Mitomycin/adverse effects , Organs at Risk/diagnostic imaging , Organs at Risk/pathology , Organs at Risk/radiation effects , Pelvis/diagnostic imaging , Proportional Hazards Models , ROC Curve , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/methods , Regression Analysis , Tumor Burden
5.
Pract Radiat Oncol ; 7(1): e51-e58, 2017.
Article in English | MEDLINE | ID: mdl-27720702

ABSTRACT

PURPOSE: Preoperative short-course radiation therapy (SCRT) has rarely been used for rectal cancer in the United States, although 2 randomized phase 3 trials demonstrate equivalence to conventional chemoradiation (CRT), and recent updates to national guidelines include this regimen as a treatment option. We sought to evaluate the efficacy and safety of preoperative SCRT followed by immediate surgery within 1 week to treat rectal cancer in the US setting. METHODS AND MATERIALS: All patients treated with preoperative SCRT (4 Gy × 5 fractions for total 20 Gy) followed by planned surgery within 1 week at our institution were retrospectively evaluated. Censored cases with ≥2 years of follow-up were included along with any disease failure or death. Patients with cM1 disease were excluded. Patients with yp stage II/III disease typically received adjuvant chemotherapy from the 1990s onwards. The primary outcomes were actuarial (Kaplan-Meier) 5-year locoregional control (LC), disease-free survival (DFS), and overall survival (OS) as well as late severe (greater than or equal to grade 3) toxicity. RESULTS: Our analysis included 202 consecutive patients with clinical stage I-III disease treated from 1977 through 2011. Median follow-up was 6.5 years (range, 2-29.2). Five-year disease outcomes were 95.9% ± 1.5% for LC, 76.4% ± 3.1% for DFS, and 84.6% ± 2.6% for OS. For patients with locally advanced rectal cancer (cT3-4 and/or cN+), 5-year LC, DFS, and OS were 95.1% ± 2.1%, 73.3% ± 4.3%, and 80.6% ± 3.7%, respectively. The late severe toxicity rate was 11.4%. CONCLUSIONS: SCRT followed by immediate surgery is a safe and effective treatment for patients with rectal cancer in the United States. Though SCRT has not been widely adopted, recent updates to the national guidelines for rectal cancer as well as financial pressures to reduce healthcare costs may lead to increased utilization of this treatment regimen in the future.


Subject(s)
Rectal Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Rectal Neoplasms/mortality , Rectal Neoplasms/surgery , Retrospective Studies
6.
Radiother Oncol ; 121(1): 79-85, 2016 10.
Article in English | MEDLINE | ID: mdl-27566894

ABSTRACT

BACKGROUND AND PURPOSE: To report outcomes and toxicities of a single-institution phase I/II study of stereotactic body radiotherapy (SBRT) in the treatment of unresectable hepatocellular cancer (HCC) and intrahepatic cholangiocarcinoma (IHC). MATERIALS AND METHODS: Patients with Child-Pugh score less than 8 were eligible. A total of 32 lesions in 26 patients were treated with SBRT. Kaplan-Meier survival analysis was performed. Toxicities were graded by CTCAEv4 criteria and response was scored by EASL guidelines. RESULTS: Median prescribed dose was 55Gy (range 40-55Gy) delivered in 5 fractions. Mean tumor diameter was 5.0cm and mean GTV was 107cc. Median follow-up was 8.8months with a median survival of 11.1months, and one-year overall survival was 45%. Overall response rate was 42% and one-year local control was 91%. Nine patients experienced a decline in Child-Pugh class following treatment, and two grade 5 hepatic failure toxicities occurred during study follow-up. CONCLUSIONS: Primary hepatic malignancies not amenable to surgical resection portend a poor prognosis, despite available treatment options. Though radiation-induced liver disease (RILD) is rare following SBRT, this study demonstrates a risk of hepatic failure despite adherence to protocol constraints.


Subject(s)
Liver Neoplasms/radiotherapy , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Dose-Response Relationship, Radiation , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prospective Studies , Radiosurgery/adverse effects , Treatment Outcome
7.
Int J Radiat Oncol Biol Phys ; 95(5): 1429-1438, 2016 08 01.
Article in English | MEDLINE | ID: mdl-27209506

ABSTRACT

PURPOSE: A prospective phase 2 trial of short-course (SC) radiation therapy (RT) with 25 Gy over 5 fractions, followed by 4 cycles of 5-fluorouracil, oxaliplatin, and leucovorin (mFOLFOX6) before surgery was recently completed at our institution. We present here the patient-reported quality of life (QOL) outcomes from this trial. METHODS AND MATERIALS: Eighty patients with cT3/T4, any N, any M rectal adenocarcinoma planned for resection were enrolled between 2009 and 2012. The QOL data were obtained prospectively using the Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire before RT, before surgery, and 1 year after surgery. The previously validated minimally importance difference (MID) method was used to measure clinically significant QOL changes in FACT-C scores for each patient across time points. We examined the role of ostomy on QOL. We also compared QOL with disease outcomes and physician-reported toxicity. RESULTS: The FACT-C questionnaire was completed by 97% of patients before RT, 85% immediately before surgery, and 62% 1 year after surgery. There was no statistically significant change in mean FACT-C scores from before treatment to after treatment. The majority of patients had either no change or an increase in QOL 1 year after treatment using the MID method. There were significant changes in QOL between patients with ostomy versus no ostomy 1 year after treatment for functional well-being (FWB) (14.81 vs 20.52, P=.018) and the colorectal cancer subscale (CCS) using the MID method (P=.004). Patients without ostomy reported stable changes in bowel control 1 year after surgery. There was no statistically significant correlation between QOL and disease recurrence, pathologic complete response, pathologic T stage downstaging, or acute/late toxicity. CONCLUSIONS: SC-RT and sequential mFOLFOX6 as preoperative therapy for rectal cancer results in stable patient-reported QOL outcomes 1 year after treatment. These findings in conjunction with previously reported oncologic outcomes support further evaluation of this regimen in a phase 3 setting.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Chemoradiotherapy/psychology , Preoperative Care/psychology , Quality of Life/psychology , Rectal Neoplasms/psychology , Rectal Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Combined Modality Therapy/psychology , Dose Fractionation, Radiation , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Patient Satisfaction , Radiotherapy Dosage , Rectal Neoplasms/diagnosis , Treatment Outcome
8.
Am J Clin Oncol ; 39(1): 1-7, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26132367

ABSTRACT

OBJECTIVE: To evaluate the outcomes and toxicity of concurrent full-dose gemcitabine and intensity-modulated radiation therapy (IMRT) for patients with borderline resectable and locally advanced pancreatic adenocarcinoma after induction chemotherapy. MATERIALS AND METHODS: From 2009 to 2012, 32 patients were treated with concurrent gemcitabine and IMRT for borderline resectable or locally advanced pancreatic adenocarcinoma. All patients received induction FOLFIRINOX or gemcitabine-based chemotherapy before chemoradiation. The radiotherapy volume was limited to the primary tumor, and the median dose was 55 Gy in 25 fractions. Gemcitabine was administered weekly during radiotherapy on days 1, 8, 22, and 29 at a median weekly dose of 800 mg/m². RESULTS: Twenty-five patients had locally advanced disease and 7 had borderline resectable disease. The median follow-up time was 14.6 months. The median progression-free and overall survival were 13.9 and 23.1 months, with a trend toward improved overall survival for patients receiving induction FOLFIRINOX compared with gemcitabine-based therapy. A radiographic complete or partial response was achieved in 13 patients (41%), with 4 (13%) having complete radiographic responses. Surgical resection was performed in 10 patients (31%)--6 patients with locally advanced disease and 4 with borderline resectable disease. Grade 3/4 hematologic toxicity during and up to 6 weeks after chemoradiation occurred in 12 patients (38%); grade 3 nonhematologic toxicity occurred in 7 patients (22%), with no grade 4 or 5 toxicity. All patients completed their radiotherapy. CONCLUSIONS: Concurrent full-dose gemcitabine and limited-field IMRT after induction chemotherapy for the treatment of borderline resectable and locally advanced pancreatic cancer is promising with acceptable toxicity rates.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Induction Chemotherapy/methods , Pancreatic Neoplasms/therapy , Radiotherapy, Intensity-Modulated/methods , Adenocarcinoma/pathology , Adult , Aged , Anemia/etiology , Camptothecin/administration & dosage , Camptothecin/therapeutic use , Capecitabine/administration & dosage , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Cisplatin/administration & dosage , Cohort Studies , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease Progression , Duodenal Ulcer/etiology , Erlotinib Hydrochloride/administration & dosage , Female , Fluorouracil/therapeutic use , Gastrointestinal Diseases/etiology , Humans , Induction Chemotherapy/adverse effects , Irinotecan , Leucovorin/therapeutic use , Male , Middle Aged , Multivariate Analysis , Neoadjuvant Therapy , Neutropenia/etiology , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Pancreatectomy , Pancreatic Neoplasms/pathology , Proportional Hazards Models , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective Studies , Thrombocytopenia/etiology , Treatment Outcome , Gemcitabine
9.
Adv Radiat Oncol ; 1(2): 94-100, 2016.
Article in English | MEDLINE | ID: mdl-28740875

ABSTRACT

PURPOSE: Locally recurrent rectal cancer may cause significant morbidity. Prior reports of rectal cancer reirradiation following local recurrence suggest treatment efficacy, with variable rates of late toxicity. Modern techniques including intensity modulated radiation therapy (IMRT) may improve the therapeutic index. We report outcomes for pelvic reirradiation as treatment for rectal cancer using IMRT. METHODS AND MATERIALS: The records of 31 patients undergoing reirradiation for rectal cancer between 2004 and 2013 were reviewed. All patients underwent IMRT using an accelerated hyperfractionation (39 Gy in 1.5-Gy fractions delivered twice daily, n=15) or once-daily fractionation technique (median dose, 30.4 Gy; range, 27-40 Gy in 15-22 fractions; n = 16). The median cumulative dose was 77 Gy (range, 59-113), and the median interval from prior pelvic radiation therapy was 39.8 months (range, 10.1-307.6). Treatment intent was palliative in 20 patients and neoadjuvant or adjuvant in 11 patients. Surgery was generally reserved for patients with an isolated local recurrence. Concurrent chemotherapy was administered for 25/31 patients, most frequently capecitabine (n=11) or continuous infusion 5-fluorouracil (n=10). RESULTS: Median follow-up was 11.3 months. The prescribed treatment was completed in 29/31 patients (93.5%). Among 18 patients with symptoms attributable to recurrent disease, successful palliation was achieved in 10/18 (55.6%). The rate of grade 2 and grade 3 acute toxicities was 32.3% and 3.2%, respectively. Local control rates at 1 and 2 years were 61.3% and 47.3%, respectively. Median overall survival was 21.9 months, and 1-year survival was 66.7% for patients who had surgical resection versus 58.7% for those who did not (P = .0802). CONCLUSIONS: Rectal cancer reirradiation using IMRT is well-tolerated in the setting of prior pelvic radiation therapy. Given significant risk of local progression, further dose escalation may be warranted for patients with life expectancy exceeding 1 year.

10.
Radiat Oncol ; 10: 159, 2015 Jul 31.
Article in English | MEDLINE | ID: mdl-26227259

ABSTRACT

BACKGROUND: Although altered protocols that challenge conventional radiation fractionation have been tested in prospective clinical trials, we still have limited understanding of how to select the most appropriate fractionation schedule for individual patients. Currently, the prescription of definitive radiotherapy is based on the primary site and stage, without regard to patient-specific tumor or host factors that may influence outcome. We hypothesize that the proportion of radiosensitive proliferating cells is dependent on the saturation of the tumor carrying capacity. This may serve as a prognostic factor for personalized radiotherapy (RT) fractionation. METHODS: We introduce a proliferation saturation index (PSI), which is defined as the ratio of tumor volume to the host-influenced tumor carrying capacity. Carrying capacity is as a conceptual measure of the maximum volume that can be supported by the current tumor environment including oxygen and nutrient availability, immune surveillance and acidity. PSI is estimated from two temporally separated routine pre-radiotherapy computed tomography scans and a deterministic logistic tumor growth model. We introduce the patient-specific pre-treatment PSI into a model of tumor growth and radiotherapy response, and fit the model to retrospective data of four non-small cell lung cancer patients treated exclusively with standard fractionation. We then simulate both a clinical trial hyperfractionation protocol and daily fractionations, with equal biologically effective dose, to compare tumor volume reduction as a function of pretreatment PSI. RESULTS: With tumor doubling time and radiosensitivity assumed constant across patients, a patient-specific pretreatment PSI is sufficient to fit individual patient response data (R(2) = 0.98). PSI varies greatly between patients (coefficient of variation >128 %) and correlates inversely with radiotherapy response. For this study, our simulations suggest that only patients with intermediate PSI (0.45-0.9) are likely to truly benefit from hyperfractionation. For up to 20 % uncertainties in tumor growth rate, radiosensitivity, and noise in radiological data, the absolute estimation error of pretreatment PSI is <10 % for more than 75 % of patients. CONCLUSIONS: Routine radiological images can be used to calculate individual PSI, which may serve as a prognostic factor for radiation response. This provides a new paradigm and rationale to select personalized RT dose-fractionation.


Subject(s)
Cell Division/radiation effects , Dose Fractionation, Radiation , Dose-Response Relationship, Radiation , Precision Medicine/methods , Algorithms , Carcinoma, Non-Small-Cell Lung/radiotherapy , Cell Hypoxia , Computer Simulation , Humans , Hydrogen-Ion Concentration , Immunologic Surveillance , Lung Neoplasms/radiotherapy , Models, Biological , Radiation Tolerance , Random Allocation , Relative Biological Effectiveness , Retrospective Studies , Tumor Burden , Tumor Microenvironment
11.
HPB (Oxford) ; 17(7): 587-93, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25800066

ABSTRACT

OBJECTIVES: Adjuvant gemcitabine with or without chemoradiation is a standard therapeutic option for patients with resected pancreatic cancer. The feasibility and toxicity of gemcitabine with docetaxel before and after 5-fluorouracil (5FU)-based chemoradiation in the adjuvant pancreatic and biliary cancer setting were investigated. METHODS: After a curative-intent resection, eligible patients with pancreaticobiliary cancers were treated with two cycles of gemcitabine and docetaxel followed by 5FU-based chemoradiation. Four weeks after completing chemoradiation, two cycles of gemcitabine and docetaxel were administered. The primary endpoint was the incidence of severe toxicities. Secondary endpoints included disease-free survival (DFS) and overall survival (OS). RESULTS: Fifty patients with pancreaticobiliary cancers were enrolled. Twenty-nine patients had pancreatic cancer whereas 21 patients had biliary tract or ampullary cancers. There was one death as a result of pneumonia, and 15% of patients experienced grade 3 or greater non-haematological toxicities. The median DFS and OS for patients with pancreatic cancer were 9.6 and 17 months, respectively, and for those with resected biliary tract cancer were 12 and 23 months, respectively. CONCLUSIONS: This combination of gemcitabine and docetaxel with chemoradiation is feasible and tolerable in the adjuvant setting. Future studies utilizing a different gemcitabine/taxane combination and schedule may be appropriate in the adjuvant treatment of both pancreatic cancer and biliary tumours.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biliary Tract Neoplasms/therapy , Biliary Tract Surgical Procedures , Carcinoma/therapy , Chemoradiotherapy, Adjuvant , Deoxycytidine/analogs & derivatives , Pancreatectomy , Pancreatic Neoplasms/therapy , Taxoids/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biliary Tract Neoplasms/mortality , Biliary Tract Neoplasms/pathology , Biliary Tract Surgical Procedures/adverse effects , Biliary Tract Surgical Procedures/mortality , Carcinoma/mortality , Carcinoma/pathology , Chemoradiotherapy, Adjuvant/adverse effects , Chemoradiotherapy, Adjuvant/mortality , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Disease-Free Survival , Docetaxel , Feasibility Studies , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Pancreatectomy/adverse effects , Pancreatectomy/mortality , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Risk Factors , Taxoids/adverse effects , Time Factors , Treatment Outcome , Gemcitabine
12.
Pract Radiat Oncol ; 5(3): 176-182, 2015.
Article in English | MEDLINE | ID: mdl-25423889

ABSTRACT

PURPOSE: The purpose of this study was to evaluate liver function after high-dose liver stereotactic body radiation therapy (SBRT) in the treatment of metastatic and primary malignancies of the liver using the Child-Pugh score classification system. METHODS AND MATERIALS: This was a retrospective analysis of 46 patients treated with SBRT for metastatic and primary malignancies of the liver. Patient, disease, prior treatment, and SBRT dosimetric factors were analyzed to correlate with decline in Child-Pugh class after liver SBRT. RESULTS: Median follow-up was 11.0 months for patients alive at last follow-up. Twenty-three patients (50%) had primary liver malignancies. Median delivered dose was 55 Gy in 5 fractions (range, 36-60 Gy in 3-6 fractions) to 1 lesion (range, 1-4 lesions) measuring 4.0 cm (range, 1.3-12.4 cm). Forty-one patients (89%) received ≥50 Gy in 3 to 6 fractions. Child-Pugh score classification was A in 42 patients (91%). Seven patients (15%) received adjuvant chemotherapy or targeted therapy. Twenty-nine patients (63%) experienced an intrahepatic recurrence after treatment. Ten patients (22%) experienced a decline in Child-Pugh class at a median of 1.6 months (range, 0.2-6 months). Eighty percent experienced a one-category decline. Only the V20, V25, V30, and V50 were correlated with decline in Child-Pugh class on univariate analysis, with V25 being most significant (P = .027). A V25 >32% was associated with a 42% incidence of Child-Pugh class decline compared with 9% for V25 ≤32 (P = .029). For primary liver malignancies, a V25 >36% was associated with a 4-fold increase in the incidence of Child-Pugh class decline (60% vs 15%, P = .021). CONCLUSIONS: Approximately one-quarter of patients experience a decline in Child-Pugh class after high-dose liver SBRT. The V25 may be an important dosimetric parameter predicting decline in liver function after treatment.


Subject(s)
Liver Neoplasms/surgery , Liver/physiology , Liver/radiation effects , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Dose-Response Relationship, Radiation , Female , Follow-Up Studies , Humans , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Male , Middle Aged , Organ Sparing Treatments/methods , Radiotherapy Dosage , Retrospective Studies , Treatment Outcome
13.
Int J Hyperthermia ; 30(5): 285-94, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25144817

ABSTRACT

PURPOSE: Unresectable chest wall recurrences of breast cancer (CWR) in heavily pretreated patients are especially difficult to treat. We hypothesised that thermally enhanced drug delivery using low temperature liposomal doxorubicin (LTLD), given with mild local hyperthermia (MLHT), will be safe and effective in this population. PATIENTS AND METHODS: This paper combines the results of two similarly designed phase I trials. Eligible CWR patients had progressed on the chest wall after prior hormone therapy, chemotherapy, and radiotherapy. Patients were to get six cycles of LTLD every 21-35 days, followed immediately by chest wall MLHT for 1 hour at 40-42 °C. In the first trial 18 subjects received LTLD at 20, 30, or 40 mg/m2; in the second trial, 11 subjects received LTLD at 40 or 50 mg/m2. RESULTS: The median age of all 29 patients enrolled was 57 years. Thirteen patients (45%) had distant metastases on enrolment. Patients had received a median dose of 256 mg/m2 of prior anthracyclines and a median dose of 61 Gy of prior radiation. The median number of study treatments that subjects completed was four. The maximum tolerated dose was 50 mg/m2, with seven subjects (24%) developing reversible grade 3-4 neutropenia and four (14%) reversible grade 3-4 leucopenia. The rate of overall local response was 48% (14/29, 95% CI: 30-66%), with. five patients (17%) achieving complete local responses and nine patients (31%) having partial local responses. CONCLUSION: LTLD at 50 mg/m2 and MLHT is safe. This combined therapy produces objective responses in heavily pretreated CWR patients. Future work should test thermally enhanced LTLD delivery in a less advanced patient population.


Subject(s)
Adenocarcinoma/therapy , Antibiotics, Antineoplastic , Breast Neoplasms/therapy , Doxorubicin/analogs & derivatives , Hyperthermia, Induced , Neoplasm Recurrence, Local/therapy , Adenocarcinoma/blood , Adult , Aged , Antibiotics, Antineoplastic/adverse effects , Antibiotics, Antineoplastic/blood , Antibiotics, Antineoplastic/pharmacokinetics , Antibiotics, Antineoplastic/therapeutic use , Breast Neoplasms/blood , Combined Modality Therapy , Doxorubicin/adverse effects , Doxorubicin/blood , Doxorubicin/pharmacokinetics , Doxorubicin/therapeutic use , Female , Humans , Maximum Tolerated Dose , Middle Aged , Neoplasm Recurrence, Local/blood , Polyethylene Glycols/adverse effects , Polyethylene Glycols/pharmacokinetics , Polyethylene Glycols/therapeutic use , Temperature , Treatment Outcome
14.
Int J Radiat Oncol Biol Phys ; 88(4): 829-36, 2014 Mar 15.
Article in English | MEDLINE | ID: mdl-24606849

ABSTRACT

BACKGROUND: Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. METHODS AND MATERIALS: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. RESULTS: 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87%). CONCLUSION: This regimen achieved response and morbidity rates that compare favorably with those of conventionally fractionated radiation therapy and concurrent chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Anal Canal , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Dose Fractionation, Radiation , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Neoplasm Staging , Neoplasm, Residual , Organ Sparing Treatments , Organoplatinum Compounds/administration & dosage , Preoperative Care/methods , Prospective Studies , Pyridines/administration & dosage , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery
15.
Int J Hyperthermia ; 30(1): 1-5, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24350642

ABSTRACT

Like other technically sophisticated medical endeavours, a hyperthermia clinic relies on skilled staffing. Physicians, physicists and technologists perform multiple tasks to ensure properly functioning equipment, appropriate patient selection, and to plan and administer this treatment. This paper reviews the competencies and tasks that are used in a hyperthermia clinic.


Subject(s)
Ambulatory Care Facilities , Hyperthermia, Induced , Humans , Hyperthermia, Induced/instrumentation , Medical Staff , Monitoring, Physiologic , Physicians , Thermometry/instrumentation , Workforce
16.
Anticancer Res ; 33(10): 4557-66, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24123031

ABSTRACT

AIM: To evaluate survival outcomes of patients in pStage II-III rectal cancer treated with adjuvant 5-fluorouracil-based radiochemotherapy and to retrospectively analyze the impact of prognostic variables on local control, metastasis-free survival and cause-specific survival. PATIENTS AND METHODS: A total of 1,338 patients, treated between 1985-2005 for locally advanced rectal cancer, who underwent surgery and postoperative 5-fluorouracil-based chemoradiation, were selected. RESULTS: The actuarial 5- and 10-year outcomes were: local control 87.0%-84.1%, disease-free survival 61.6%-52.1%, metastasis-free survival 72.0%-67.2%, cause-specific survival 70.4%-57.5%, and overall survival 63.8%-53.4%. Better outcomes were observed in patients with IIA, IIIA stage. Multivariate analyses showed that variables significantly affecting metastasis-free survival were pT4 and pN2, while for cancer-specific survival those variables were age >65 years, pT4, pN1, pN2, distal tumors and number of lymph nodes removed ≤ 12. CONCLUSION: This study confirmed that among stage II-III rectal cancer patients there are subgroups of patients with different clinical outcomes.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Fluorouracil/therapeutic use , Rectal Neoplasms/therapy , Chemoradiotherapy , Disease-Free Survival , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Postoperative Period , Prognosis , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Retrospective Studies , Treatment Outcome
18.
Mol Imaging Biol ; 15(1): 106-13, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22684813

ABSTRACT

PURPOSE: This pilot study was performed to evaluate whether tumor uptake of (18)F-labeled 3'-deoxy-3'fluorothymidine (FLT), a proliferative radiotracer, at baseline and early during therapy, is predictive of outcome in locally advanced rectal cancer. PROCEDURES: Fourteen patients underwent positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and FLT before therapy and PET with FLT approximately 2 weeks after initiating neoadjuvant chemoradiotherapy. FLT and FDG uptake were evaluated qualitatively and by maximum standardized uptake value (SUV(max)). Tumor FLT and FDG uptake were correlated with disease-free survival (DFS). RESULTS: Thirteen patients underwent surgery after therapy, one died before surgery with progressive disease. FDG-PET/computed tomography detected regional lymph node metastases in five and FLT-PET was positive in one. High pretherapy FDG uptake (SUV(max) ≥ 14.3), low during-therapy FLT uptake (SUV(max) < 2.2), and high percentage change in FLT uptake (≥60 %) were predictive of improved DFS (p < 0.05 for all three values). CONCLUSION: Pretherapy FDG uptake, during-therapy FLT uptake, and percentage change in FLT uptake were equally predictive of DFS.


Subject(s)
Dideoxynucleosides , Positron-Emission Tomography/methods , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/therapy , Adult , Aged , Chemoradiotherapy, Adjuvant , Dideoxynucleosides/chemistry , Dideoxynucleosides/pharmacokinetics , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoadjuvant Therapy , Pilot Projects , Predictive Value of Tests , Prognosis , Rectal Neoplasms/diagnosis , Rectal Neoplasms/metabolism , Treatment Outcome
19.
Int J Radiat Oncol Biol Phys ; 86(1): 27-33, 2013 May 01.
Article in English | MEDLINE | ID: mdl-23154075

ABSTRACT

PURPOSE: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. METHODS AND MATERIALS: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤ 3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator's ability to perform DP-IMRT. RESULTS: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. CONCLUSIONS: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Anus Neoplasms/therapy , Carcinoma, Squamous Cell/therapy , Carcinoma, Transitional Cell/therapy , Chemoradiotherapy/methods , Radiotherapy, Intensity-Modulated/methods , Adult , Aged , Aged, 80 and over , Anal Canal , Analysis of Variance , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Anus Neoplasms/diagnostic imaging , Anus Neoplasms/pathology , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Carcinoma, Transitional Cell/pathology , Chemoradiotherapy/adverse effects , Dose Fractionation, Radiation , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Gastrointestinal Tract/radiation effects , Humans , Male , Middle Aged , Mitomycin/administration & dosage , Mitomycin/adverse effects , Neoplasm Staging , Radiation Injuries/prevention & control , Radiography , Radiotherapy Planning, Computer-Assisted/standards , Radiotherapy, Intensity-Modulated/adverse effects , Urogenital System/radiation effects
20.
Med Phys ; 39(11): 6838-46, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23127076

ABSTRACT

PURPOSE: To present design aspects and acceptance tests performed for clinical implementation of electronic brachytherapy treatment of early stage rectal adenocarcinoma. A dosimetric comparison is made between the historically used Philips RT-50 unit and the newly developed Axxent(®) Model S700 electronic brachytherapy source manufactured by Xoft (iCad, Inc.). METHODS: Two proctoscope cones were manufactured by ElectroSurgical Instruments (ESI). Two custom surface applicators were manufactured by Xoft and were designed to fit and interlock with the proctoscope cones from ESI. Dose rates, half value layers (HVL), and percentage depth dose (PDD) measurements were made with the Xoft system and compared to historical RT-50 data. A description of the patient treatment approach and exposure rates during the procedure is also provided. RESULTS: The electronic brachytherapy system has a lower surface dose rate than the RT-50. The dose rate to water on the surface from the Xoft system is approximately 2.1 Gy∕min while the RT-50 is 10-12 Gy∕min. However, treatment times with Xoft are still reasonable. The HVLs and PDDs between the two systems were comparable resulting in similar doses to the target and to regions beyond the target. The exposure rate levels around a patient treatment were acceptable. The standard uncertainty in the dose rate to water on the surface is approximately ±5.2%. CONCLUSIONS: The Philips RT-50 unit is an out-of-date radiotherapy machine that is no longer manufactured with limited replacement parts. The use of a custom-designed proctoscope and Xoft surface applicators allows delivery of a well-established treatment with the ease of a modern radiotherapy device. While the dose rate is lower with the use of Xoft, the treatment times are still reasonable. Additionally, personnel may stand farther away from the Xoft radiation source, thus potentially reducing radiation exposure to the operator and other personnel.


Subject(s)
Brachytherapy/instrumentation , Equipment Design , Humans , Radiometry , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted
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