Dose-painted Intensity Modulated Radiation Therapy Research Articles

ASO Visual Abstract: Feasibility of Preoperative Dose-Painting Intensity-Modulated Radiation Therapy (IMRT) for Borderline Resectable Primary Retroperitoneal Sarcoma.

ASO Visual Abstract: Feasibility of Preoperative Dose-Painting Intensity-Modulated Radiation Therapy (IMRT) for Borderline Resectable Primary Retroperitoneal Sarcoma.

Feasibility of Preoperative Dose-Painting Intensity Modulated Radiation Therapy (IMRT) for Borderline-Resectable Primary Retroperitoneal Sarcoma.

The role of radiation therapy (RT) in resectable retroperitoneal sarcoma (RPS) remains controversial; however, preoperative RT may play an important role in borderline-resectable (at risk of R2 resection) disease. We evaluated the outcome of such patients treated with preoperative dose-painting IMRT followed by planned resection. Between January 2001 and December 2017, 30 patients with borderline-resectable primary nonmetastatic RPS (after multidisciplinary review) received preoperative dose-painting IMRT in this retrospective cohort study. Median follow-up for all patients was 32 months. Median dose to the whole tumor/high-risk margin was 50.4 Gy/60.2 Gy. Sixteen patients were female, 24 were >50 years. Median tumor size was 9.2 cm. After RT, 6 did not have surgery. Of the 24 who were explored, 20 underwent complete gross resection. During RT, 7 of 30 patients developed acute grade 2+ toxicities: 5 fatigue, 1 nausea and vomiting, and 1 cystitis. RT was completed in 29 of 30 patients. Postoperatively, 12 of 20 patients developed grade 2+ complications: 2 gastropathy, 5 intraabdominal collections requiring drainage, 1 retroperitoneal bleed, and 3 delayed wound healing. Late grade 2+ toxicity was observed in 3 of 20 patients: 1 lymphedema with recurrent cellulitis, 1 chronic diarrhea, 1 gastrointestinal bleeding from anastomosis requiring transfusions, and 2 renal insufficiency. In those who underwent complete gross resection (n = 20, median follow-up 47 months), the 5-year local control was 57%, and overall survival was 46%. Preoperative dose-painting IMRT given to borderline-resectable RPS rendered 67% of patients resectable, provided a 5-year local control rate of 57%, which is similar to those with resectable disease, and had an acceptable morbidity profile.

Diffusion-Weighted Magnetic Resonance Imaging-Guided Dose Painting in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma Treated With Induction Chemotherapy Plus Concurrent Chemoradiotherapy: A Randomized, Controlled Clinical Trial

We hypothesized that diffusion-weighted magnetic resonance imaging (DWI)-guided dose-painting intensity modulated radiation therapy (DP-IMRT) is associated with improved local tumor control and survival in locoregionally advanced nasopharyngeal carcinoma (NPC). The purpose of this randomized study was to compare the efficacy and toxicity of DWI-guided DP-IMRT to conventional magnetic resonance imaging (MRI)-based IMRT in locoregional advanced NPC. A total of 260 patients with stage III-IVa NPC disease were randomly assigned in a 1:1 ratio to receive induction chemotherapy followed by chemoradiotherapy by DWI-guided DP-IMRT (group A, n=130) or conventional MRI-based IMRT (group B, n=130) in this prospective clinical trial. In group A, subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC < mean) according to MRI before induction chemotherapy. The dose to GTVnx-DWI was escalated to 75.2 Gy/32 fx in patients with T1-2 disease and to 77.55 Gy/33 fx in those with T3-4 disease in 2.35 Gy per fraction. In group B, planning gross tumor volumeof nasopharynx was irradiated at 70.4 to 72.6 Gy/32 to 33 fx in 2.2 Gy per fraction. This trial is registered with chictr.org.cn (ChiCTR1800015779). A total of 260 patients were included in the trial (130 patients in group A and 130 in group B). Complete response rates after chemoradiotherapy were 99.2% (129 of 130) and 93.8% (122 of 130) in groups A and B, respectively (P=.042). At a median follow-up of 25 months, DWI-guided DP-IMRT was associated with improved 2-year disease-free survival (DFS; 93.6% [95% confidence interval {CI}, 88.1%-99.1%] vs 87.5% [95% CI, 81.4%-93.6%], P=.015), local recurrence-free survival (100% [95% CI, not applicable {NA}] vs 91.3% [95% CI, 85.4%-97.2%]), locoregional recurrence-free survival (LRRFS; 95.8% [95% CI, NA] vs 91.3% [95% CI, 85.4%-97.2%]), distant metastasis-free survival (DMFS; 97.8% [95% CI, NA] vs 90.9% [95% CI, 85.8%-96.0%]), and overall survival (100% [95% CI, NA] vs 94.5% [95% CI, 89.2%-99.8%]). Zero and 3 patients had local-only recurrences in group A and B, respectively. The most common site of first failure in each arm was distant organ failure. No statistically significant differences in acute and late toxic effects were observed. Multivariate analyses showed that DP (DWI-guided DP-IMRT vs conventional MRI-based IMRT without DP) was associated with DFS, local recurrence-free survival, LRRFS, and distant metastasis-free survival. Epstein-Barr virus DNA level was associated with DFS and LRRFS. DWI-guided DP-IMRT plus chemotherapy is associated with a disease-free survival benefit compared with conventional MRI-based IMRT among patients with locoregionally advanced NPC without increasing acute toxic effects.

Long-Term Outcomes of NRG Oncology/RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Anal Canal Cancer

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. 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. 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. 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.

Feasibility of Preoperative Dose-Painting Intensity Modulated Radiation Therapy (IMRT) for Borderline Resectable/Unresectable Primary Retroperitoneal Sarcoma

Feasibility of Preoperative Dose-Painting Intensity Modulated Radiation Therapy (IMRT) for Borderline Resectable/Unresectable Primary Retroperitoneal Sarcoma

Positron Emission Tomography–Adjusted Intensity Modulated Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

Toperform a prospective trial examining positron emission tomography (PET)-based, dose-painted intensity modulated radiation therapy (IMRT) in the setting of locally advanced non-small cell lung cancer (NSCLC). Patients with stage IIB-III NSCLC were treated with 25 fractions of dose-painted IMRT. Tumors or lymph nodes with metabolic tumor volume exceeding 25cm3 were deemed "high risk" and received 65Gy. Smaller lesions were treated with 57Gy or 52.5Gy (after November 2014). Patients received concurrent weekly carboplatin (area under the curve=2) and paclitaxel (45mg/m2). The primary study endpoint was the absence of high residual metabolic activity (maximum standardized uptake value>6) in treated lesions on PET 12 to 16weeks after completion of IMRT. Thirty-five subjects with 116 hypermetabolic lesions were eligible for analysis. The primary endpoint was met for 24 of 30 patients (80%) who underwent posttreatment PET, satisfying our efficacy objective. With a median follow-up duration of 23.8months for living patients, progression in a lesion targeted with radiation therapy has been observed in 5 patients (14%). Treating progression in other sites and death without progression as competing risks, 2-year cumulative incidence rates of local disease progression in high-risk lesions (n=24) and low-risk lesions (n=92) are 9% and 3%, respectively. The actuarial rate of overall survival at 2years is 52%. Dose-painted IMRT based on pretreatment PET metrics with concurrent chemotherapy yields high rates of metabolic response and local disease control for locally advanced NSCLC. Future trials should test this approach to maximize the therapeutic ratio of thoracic radiation therapy.

NRG Oncology/RTOG 0529: Long-Term Outcomes of Dose-Painted Intensity Modulated Radiation Therapy, 5-Fluorouracil, and Mitomycin-C in Anal Canal Cancer

NRG Oncology/RTOG 0529: Long-Term Outcomes of Dose-Painted Intensity Modulated Radiation Therapy, 5-Fluorouracil, and Mitomycin-C in Anal Canal Cancer

Predictors of Radiation Therapy–Related Gastrointestinal Toxicity From Anal Cancer Dose-Painted Intensity Modulated Radiation Therapy: Secondary Analysis of NRG Oncology RTOG 0529

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). 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 60Gy(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). 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 >4cm, and worse Zubrod performance status. Small bowel volumes of 186.0cc, 155.0cc, 41.0cc, and 30.4cc receiving doses greater than 25, 30, 35, and 40Gy, respectively, correlated with increased risk of acute grade ≥2 GI AEs. 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.

Long-term outcomes and toxicities of a large cohort of anal cancer patients treated with dose-painted IMRT per RTOG 0529

PurposeTo describe the outcomes and toxicities of the largest cohort to date of patients with anal squamous cell carcinoma uniformly treated with concurrent chemoradiation using dose-painted intensity modulated radiation therapy (DP-IMRT) according to RTOG 0529. Methods and materialsWe identified 99 eligible patients with anal cancer who were treated at our institution with definitive chemoradiation using DP-IMRT between 2005 and 2015 per RTOG 0529 dosing guidelines. Primary study endpoints included event-free survival (defined as recurrence, colostomy, or death) and overall survival. Secondary endpoints were treatment duration and acute and late toxicity. ResultsAt a median follow-up of 49 months (range, 2-114 months), 92% of patients had a clinical complete response. Fifteen percent underwent colostomy, including 4 pretreatment colostomies, 6 planned abdominoperineal resections (APRs), 4 salvage APRs, and 1 APR for treatment-related complications. Thirteen patients developed local recurrence, of whom 6 developed synchronous metastatic disease. The 4-year overall survival was 85.8%, and 4-year event-free survival was 75.5%. Median treatment duration was 43 days (range, 10-68 days). The overall rate of non-hematologic grade 3+ acute and grade 2+ late toxicities was 20% and 15%, respectively. ConclusionsLong-term outcomes and tolerability were excellent In the largest cohort to date of patients with anal cancer who received DP-IMRT prescribed per RTOG 0529.

PET/CT-guided dose-painting versus CT-based intensity modulated radiation therapy in locoregional advanced nasopharyngeal carcinoma

BackgroundThe effect of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)-guided dose-painting intensity-modulated radiation therapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. This study aimed to assess the efficacy and toxicity of such combination.MethodsFrom 2012 to 2014, 213 patients with stage III-IVB NPC received chemoradiotherapy by PET/CT-guided DP-IMRT (group A, n = 101) or CT-based IMRT (group B, n = 112). In group A, subvolume GTVnx-PET (gross tumor volume of nasopharynx in PET images) was defined within GTVnx (gross tumor volume of nasopharynx) as the SUV50%max isocontour; the dose to GTVnx-PET was escalated to DT 75.2 Gy/32 and 77.55 Gy/33 Fx, respectively, for patients with T1-2 and T3-4 disease, respectively. In group B, PGTVnx was irradiated at DT 70.4–72.6 Gy/32–33 Fx in 2.2 Gy per fraction.ResultsComplete response rates were 99.0% (100/101) and 92.9% (104/112) in groups A and B, respectively (P = 0.037). Compared with CT-based IMRT, FDG-PET/CT guided DP-IMRT significantly improved 3-year local failure-free survival (LFFS, 98.8% vs. 91.3%; P = 0.032), locoregional failure-free survival (LRFFS, 97.2 vs. 91.2%; P = 0.049), distant metastasis-free survival (DMFS, 92.9% vs. 87.4%; P = 0.041), disease free survival (DFS, 87.9% vs. 82.4%; P = 0.02), and overall survival (OS, 91.8% vs. 82.6%; P = 0.049). No statistically significant differences in acute and late toxic effects were observed. Multivariate analysis showed that dose painting (PET/CT-guided DP-IMRT vs CT-based IMRT without DP) was a significant independent prognostic factor for LFFS and DFS.ConclusionFDG-PET/CT guided DP-IMRT plus chemotherapy is associated with a considerable survival benefit, without increasing toxicity in patients with locoregional advanced NPC. Further randomized trials are needed to fully assess the role of PET/CT-guided DP-IMRT.

Cost-Effective Analysis of Hypofractionated Versus Standard 30-Fraction IMRT in Patients With Poor Prognosis Glioblastoma Multiforme

We previously reported the tolerability and outcome of hypofractionated radiation therapy (HFRT) using dose painting intensity-modulated radiation therapy (IMRT) 36 Gy and 24 Gy in 6 fractions (fx) every-other-day over 2 weeks with concurrent and adjuvant temozolomide in glioblastoma multiforme (GBM) patients with especially poor prognoses. This study aims to evaluate the cost-effectiveness of radiation therapy (RT) for 6-fx HFRT compared to the standard of 30-fx RT to 60 Gy over 6 weeks, both using IMRT technique.

Predictors of Radiotherapy-Related GI Toxicity from Anal Cancer DP-IMRT: Secondary Analysis of RTOG 0529

Radiation Therapy Oncology Group (RTOG) 0529 assessed the feasibility of dose-painted intensity-modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5-FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient (pt) and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs).

Predictors of radiotherapy-related gastrointestinal toxicity from anal cancer DP-IMRT: Secondary analysis of RTOG 0529.

460 Background: Radiation Therapy Oncology Group (RTOG) 0529 assessed 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 (pt) and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). Methods: RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel (SB), loosely contoured anterior pelvic contents (APC), and uninvolved portions of colon outside the clinical target volume (UC). T-tests were performed to evaluate differences in the mean absolute volumes of each critical structure receiving doses ≥ 5 to 60 Gy (V5-V60) in 5 Gy increments between pts with and without ≥ grade (G) 2, acute and late GI AEs, and ≥G3 acute GI AEs using the NCI Common Terminology Criteria, version 3. Acute is defined as ≤ 90 days from the start of treatment and late is &gt; 90 days. Additional factors (age, location, gender, race, Zubrod, grade, size, stage, prone vs supine position) were also evaluated in multivariate (MV) logistic regression (acute AEs) or Cox proportional hazards models (late AEs) to evaluate correlation with GI AEs. Results: Among 52 evaluable pts, ≥G2 acute, ≥G2 late, and ≥G3 acute GI AEs were observed in 35, 17, and 10 pts, respectively. Trends (p&lt;0.05) towards statistically significant associations were observed between: ≥G2 acute GI AEs and SB dose (V20-V40); ≥G2 late GI AEs and APC dose (V60); ≥G3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size &gt;4cm, and worse Zubrod. SB and APC dose parameters remained correlated with GI AEs on MV analysis. Treatment in the prone vs supine position correlated with lower SB V10-V35 and APC V5-V20, although no significant differences in GI AEs were observed. Conclusions: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlates with RT dose to the SB and APC. Further analysis is underway to determine critical structure cut-point parameters that may aid treatment plan optimization for anal cancer DP-IMRT. Supported by RTOG U10 CA21661, CCOP U10 CA3742 and ATC U24 CA 81647 NCI grants. Clinical trial information: NCT00423293.

Dose escalation using dose-painted IMRT in locally advanced rectal cancer.

582 Background: After preoperative chemo-radiation, clinical response and tumor pathologic downstaging showed a close correlation with improved outcomes. We report our initial experience in dose escalation using dose-painted intensity-modulated radiation therapy (DP-IMRT) in patients with locally advanced rectal cancer. Methods: Fifteen patients with locally advanced rectal cancer (T3-4,N0-1) were prospectively identified. Tumors were staged using the cTNM classification by PET/CT, EUS &amp; MRI. All received preoperative 5-FU and DP-IMRT. Doses were prescribed as follows:56 Gy/2.0 Gy fractions (fxn) to the planning target volume (PTV) and 47.6Gy/1.7Gyfxn to elective nodal PTV. Surgery was performed 6-8 weeks after chemo-radiation. The surgical procedure was tailored to tumor downstaging. The choice of sphincter-preserving surgery was based on the distance between the lower tumor pole and the anorectal ring “ after” chemoradiation. All were reevaluated for tumor response, preoperatively by imaging studies (ycTNM) and by pathological staging (ypTN) following surgery. Acute and late toxicities were monitored by the treating physician. Results: All patients completed therapy. Tumors were in the lower 1/3 in 3 patients, middle 1/3 in 7, and upper 1/3 in 5. With preoperative endorectal US, PET/CT and MRI, the clinical staging of the tumors was: 13 (T3N0) and 2 (T4N0). Acute toxicity was limited to a moderate proctitis (RTOG acute toxicity scoring system, G1 ) in all patients, with two patients with tumors extending into the anal canal having G 3 dermatitis. Complete clinical response was obtained in 10 of 15 patients.All 15 underwent surgery; 6 had pathological pT0N0, 4 had residual micro foci of carcinoma (pT1N0), and 5 had residual disease limited to the muscularis propria (pT2N0). No difference in perioperative complications was seen. Conclusions: Preoperative dose-escalation using dose-painted radiation therapy (DP-IMRT) seems to be safe. Moderate local acute toxicity was seen with very low-lying tumors. This modality provides a high rate of tumor downsizing especially for patients with lesions in the lower 2/3 of the rectum with a possible potential for an increased ability to perform sphincter-preserving surgery.

RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Carcinoma of the Anal Canal

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. 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. 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. 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.

Dose-painted Intensity Modulated Radiation Therapy for Anal Cancer: No Differences in Treatment Toxicity and Early Outcomes Between Human Immunodeficiency Virus Positive and Negative Patients

HIV infected patients are reported to experience increased treatment toxicity with non-conformal radiation and concurrent chemotherapy for anal cancer. We report our multi-institutional analysis of toxicity and two-year outcomes utilizing dose-painted intensity-modulated radiation therapy (DP-IMRT) in HIV positive (HIV+) patients on highly active antiretroviral therapy (HAART).

Dose-Painting Intensity Modulated Radiation Therapy for Pediatric Sarcomas With Lung Metastases

Dose-Painting Intensity Modulated Radiation Therapy for Pediatric Sarcomas With Lung Metastases

Dose-painted Intensity Modulated Radiation Therapy May Offer Improved Morbidity as Compared to 3D-CRT

Dose-painted Intensity Modulated Radiation Therapy May Offer Improved Morbidity as Compared to 3D-CRT

Dose-Painted Intensity Modulated Radiation Therapy Improves Local Control for Locally Advanced Pancreas Cancer

Background. To evaluate the outcomes, adverse events, and therapeutic role of Dose-Painted Intensity-Modulated Radiation Therapy (DP-IMRT) for locally advanced pancreas cancer (LAPC). Methods. Patients with LAPC were treated with induction chemotherapy (n = 25) and those without metastasis (n = 20) received DP-IMRT consisting of 45 Gy to Planning Treatment Volume 1 (PTV1) including regional lymph nodes with a concomitant boost to the PTV2 (gross tumor volume + 0.5 cm) to either 50.4 Gy (n = 9) or 54 Gy (n = 11) in 25 fractions. DP-IMRT cases were compared to three-dimensional conformal radiation therapy (3D-CRT) plans to assess the potential relationship of radiation dose to adverse events. Kaplan-Meier and Cox regression analyses were used to calculate survival probabilities. The Fisher exact test and t-test were utilized to investigate potential prognostic factors of toxicity and survival. Results. Median overall and progression-free survivals were 11.6 and 5.9 months, respectively. Local control was 90%. Post-RT CA-19-9 levels following RT were predictive of survival (P = 0.02). Grade 2 and ≥grade 3 GI toxicity were 60% and 20%, respectively. In comparison to 3D-CRT, DP-IMRT plans demonstrated significantly lower V45 values of small bowel (P = 0.0002), stomach (P = 0.007), and mean liver doses (P = 0.001). Conclusions. Dose-escalated DP-IMRT offers improved local control in patients treated with induction chemotherapy for LAPC. Radiation-related morbidity appears reduced with DP-IMRT compared to 3D-CRT techniques, likely due to reduction in RT doses to organs at risk.

Dose-painted intensity-modulated radiation therapy (DP-IMRT) for anal cancer: No differences in treatment toxicity and early outcomes between human immunodeficiency virus (HIV) positive and negative patients.

565 Background: HIV-infected patients are reported to experience increased treatment toxicity with standard concurrent chemoradiation (CRT) protocols for anal cancer. IMRT is a novel radiation (RT) delivery technique that allows the oncologist to conform or “dose paint (DP)” the RT dose to the tumor while sparing surrounding normal organs. We report our multi-institutional experience with DP-IMRT in regards to acute toxicities and treatment outcomes in HIV positive (HIV+) patients on highly active antiretroviral therapy (HAART). Methods: From August 2005 to December 2010, 63 patients, (10 HIV+), were treated with CRT for biopsy-proven, squamous cell carcinoma of the anal canal at two academic medical centers. HIV+ and HIV- patients received a median DP-IMRT dose of 50.4 Gy over 43.5 and 42.0 days, respectively. Acute toxicities were graded according to the NCI Common Terminology Criteria for Adverse Events, version 3.0. Two year actuarial control and survival rates were calculated using the Kaplan-Meier method. Results: The median follow-up was 29.3 and 24.3 months for HIV+ and HIV- patients, respectively. No significant differences were noted in acute grade 3+ toxicity in HIV+ versus HIV- patients: dermatologic 10.0% vs. 13.21%, p=1.0; genitourinary 10.0% vs. 3.77%, p=0.410; gastrointestinal 20.0% vs. 15.09%, p=0.653; and hematologic 80.0% vs. 64.15%, p=0.474. Multivariate analysis confirmed that HIV infection was not predictive of acute grade 3/4 toxicity. No significant differences were noted in 2-year local control (90.0% vs. 95.0%), distant control (90.0% vs. 89.7%), overall survival (90.0% vs. 89.2%), and colostomy-free survival (90.0% vs. 83.7%) rates among HIV+ vs. HIV- patients. Conclusions: HIV+ patients on HAART receiving concurrent chemotherapy with DP-IMRT for anal canal cancer showed similar two-year outcomes and no significant differences in acute toxicity compared to HIV- patients. As such, HIV+ patients with anal cancer should be considered eligible for all national trials in which IMRT is employed.