Two-year outcomes of RTOG 0529: A phase II evaluation of dose-painted IMRT in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 368-368 ◽  
Author(s):  
L. A. Kachnic ◽  
K. A. Winter ◽  
R. J. Myerson ◽  
M. D. Goodyear ◽  
J. Willins ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Anal Canal ◽  
Mitomycin C ◽  
Anal Cancer ◽  
Second Primary ◽  
Anal Canal Cancer ◽  
Kaplan Meier ◽  
Conventional Radiation ◽  
Target Volumes ◽  
Grade 3

368 Background: 5-Fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer is associated with high rates of acute morbidity. We have previously shown that dose-painted IMRT (DP-IMRT) significantly reduces grade 3+ GI and dermatologic acute toxicity, as compared to the RTOG 9811 5FU/MMC arm, which used non-conformal radiation techniques. We now report on the two-year outcomes of this DP-IMRT approach. Methods: T2-4N0-3M0 anal canal cancers received 5FU (1,000 mg/m2/day 96 hour infusion) and MMC (10 mg/m2 bolus) days 1 and 29 of DP-IMRT prescribed as follows - T2N0: 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs), 28 fractions; T3-4N0-3: 45 Gy elective nodal, 50.4 Gy ≤ 3 cm and 54 Gy > 3 cm metastatic nodal and 54 Gy anal tumor PTVs, 30 fractions. The following two-year outcomes were assessed: local-regional (LRF) and colostomy failures (CF) using the cumulative incidence method, and disease-free (DFS), overall (OS) and colostomy-free survivals (CFS) using the Kaplan-Meier method. Results: Of 63 accrued patients, 52 were analyzable. Median age was 58 years; 81% female; 54% stage II; 25% IIIA; 21% IIIB. Median follow-up was 23.2 months (0.2-33). Two-year LRF, CF, DFS and 95% confidence intervals are 20% (9%, 31%), 8% (0.4%, 15%) and 77% (62%, 86%), respectively. The causes of death for the 7 patients that died are: anal cancer in 5, morbidity in one and second primary outside the radiation field in one. Two-year comparison data from the RTOG 9811 5FU/MMC arm are shown in the table below. Conclusions: DP-IMRT with 5FU/MMC for the treatment of anal canal cancer yields similar two-year outcomes as the RTOG 9811 conventional radiation, 5FU/MMC arm. Because of the associated acute toxicity sparing, DP-IMRT will be used as the platform, and may allow for radiation dose escalation, in future RTOG anal canal trials. Supported by RTOG U10 CA21661, CCOP U10 CA3742 and ATC U24 CA 81647 NCI grants. [Table: see text] No significant financial relationships to disclose.

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.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 565-565 ◽  
Author(s):  
Paul B. Romesser ◽  
Joseph D. Mancias ◽  
Muhammad M. Qureshi ◽  
Kevan L. Hartshorn ◽  
John D. Willins ◽  
...  
Keyword(s):  
Anal Canal ◽  
Anal Cancer ◽  
Highly Active Antiretroviral Therapy ◽  
Concurrent Chemotherapy ◽  
Hiv Positive ◽  
Anal Canal Cancer ◽  
Hiv Patients ◽  
Treatment Toxicity ◽  
Delivery Technique ◽  
Grade 3

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.

A pilot feasibility study of definitive concurrent chemoradiation with pencil beam scanning proton beam in combination with 5-fluorouracil and mitomycin-c for carcinoma of the anal canal.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 733-733
Author(s):  
Jennifer Yon-Li Wo ◽  
Beow Y. Yeap ◽  
Thomas F. DeLaney ◽  
David P. Ryan ◽  
Aparna Raj Parikh ◽  
...  
Keyword(s):  
Pilot Study ◽  
Anal Canal ◽  
Proton Beam ◽  
Mitomycin C ◽  
Anal Cancer ◽  
Pencil Beam ◽  
Pencil Beam Scanning ◽  
Dermatologic Toxicity ◽  
Grade 3

733 Background: Definitive chemoradiation (CRT) with concurrent 5-fluorouracil (5-FU)/mitomycin C (MMC) for anal cancer yields high rates of long term survival. However, CRT has significant acute and long term toxicity. Pencil beam scanning proton beam (PBS-PT) may potentially reduce this toxicity. This is a pilot study evaluating the feasibility of definitive concurrent CRT with PBS-PT with 5-FU/MMC for anal cancer. Methods: Pts were enrolled on an NCI sponsored, prospective, multi-institutional, pilot study (NCT 01858025). Key eligibility were ECOG 0-2, age 18+, invasive SCC of the anal canal, clinically staged T1-4, N0-3. Pts were treated per RTOG 0529 RT schema; for T1-2, N0: 50.4 Gy to primary CTV, 42 Gy to elective LNs; for T3+ or N+: 54 Gy to primary CTV, 50.4-54 Gy to involved LN, and 45 Gy to elective LNs. Pts received 5-FU/MMC on day 1 and 29. The primary objective of this study was to determine feasibility of PBS-PT with 5-FU/MMC, determined if grade 3+ dermatologic toxicity is < 48% (grade 3+ dermatologic toxicity from RTOG 98-11). The secondary endpoint was rates of overall grade 3+ toxicities, clinical complete response (cCR) rate and patterns of local regional tumor recurrence. Results: Between February 2014 to April 2017, we enrolled 25 patients into our study, all of whom were analyzed. 23 pts (92%) completed treatment per protocol, 2 pts died on treatment due to underlying comorbidities. Median time to completion of treatment was 42 days (range 38-49). The Grade 3+ radiation dermatitis was 24% (Table 1). With a median follow-up of 17.6 months (range 7.7-42.0) among the 21 patients still alive, the 1 year local control, progression-free survival, and overall survival are 100%, 83% and 87%, respectively. Conclusions: In our prospective, pilot study of PBS-PT with concurrent 5-FU/MMC, PBS-PT was found to be feasible. While felt to be unrelated to the study, the two Grade 5 adverse events on this small study highlights potentially treatment related risks of this effective yet toxic regimen. Clinical trial information: NCT01858025. [Table: see text]

Induction Therapy for Poor-Prognosis Anal Canal Carcinoma: A Phase II Study of the Cancer and Leukemia Group B (CALGB 9281)

2008 ◽  
Vol 26 (19) ◽  
pp. 3229-3234 ◽  
Author(s):  
Neal J. Meropol ◽  
Donna Niedzwiecki ◽  
Brenda Shank ◽  
Thomas A. Colacchio ◽  
John Ellerton ◽  
...  
Keyword(s):  
Anal Canal ◽  
Mitomycin C ◽  
Poor Prognosis ◽  
Combined Modality Therapy ◽  
Induction Treatment ◽  
Anal Canal Cancer ◽  
Combined Modality ◽  
Bulky N2 ◽  
Disease Free ◽  
Patients With Poor Prognosis

PurposeAlthough most patients with anal canal cancer are cured with sphincter-preserving, nonsurgical, combined-modality therapy, those with large tumors and lymph node involvement have a poor prognosis. To establish the safety and efficacy of induction chemotherapy with infusional fluorouracil (FU) plus cisplatin followed by FU plus mitomycin C with concurrent radiation in patients with poor-prognosis squamous cell cancers of the anal canal.MethodsPatients with previously untreated anal canal cancers with T3 or T4 tumors and/or extensive nodal involvement (bulky N2 or N3) received two 28-day cycles of induction treatment with infusional FU plus cisplatin followed by two 28-day cycles of FU plus mitomycin C with concurrent split-course radiation. A third cycle of FU and cisplatin with radiation boost was given to patients with persistent primary site disease or bulky N2 or N3 disease at presentation.ResultsForty-five assessable patients received protocol therapy. Treatment was generally well tolerated, and gastrointestinal and hematologic toxicities were the most common. Induction chemotherapy resulted in eight complete and 21 partial responses. After induction, combined-modality, and boost therapy, 37 (82%) of 45 assessable high-risk patients achieved a complete response. After 4 years of follow-up, 68% of patients are alive, 61% are disease-free, and 50% are colostomy- and disease-free.ConclusionA combined-modality approach that includes induction treatment with FU and cisplatin followed by combined-modality therapy with FU, mitomycin C, and concurrent radiation results in long-term disease control in the majority of patients with poor-prognosis anal canal cancer.

Comparison of acute toxicity in patients treated with a 4-field box or IMRT to deliver elective pelvic nodal irradiation for localized high-risk prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 69-69
Author(s):  
Suneil Jain ◽  
Patrick Cheung ◽  
D. Andrew Loblaw ◽  
Gerard Morton ◽  
Cyril Danjoux ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Acute Toxicity ◽  
Urinary Frequency ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Target Volumes ◽  
Common Technique ◽  
Grade 3 ◽  
New Literature

69 Background: To deliver elective pelvic nodal irradiation (EPNI), a 4-field box (4FB) has been a common technique. More recently, there are increasing reports of using IMRT to deliver EPNI. Even though studies show a clear dosimetric benefit to bowel and bladder, there is a lack of good data demonstrating decreased toxicity with the use of IMRT in this setting. Methods: From 2004-2010, 230 patients with localized high risk prostate cancer were enrolled into 3 sequential prospective phase I/II trials of delivering EPNI (45 Gy) along with a concomitant hypofractionated IMRT boost to the prostate (67.5 Gy total) in 25 fractions over 5 weeks time. All patients were to receive 3 years of adjuvant androgen deprivation. During the accrual period, the method used to deliver the EPNI portion of the treatment changed as new literature emerged about target volumes for EPNI. The 3 methods used to deliver EPNI in this large cohort were 1) 4FB, 2) IMRT with 2cm CTV margins around the pelvic vessels as suggested by Shih et al (IMRT-Shih), and 3) IMRT with nodal volumes as suggested by RTOG (IMRT-RTOG). Common Terminology Criteria for Adverse Events v3.0 was used to assess acute toxicity prospectively during treatment and then at 3 months. Results: For EPNI, 94 patients were treated with a 4FB, 53 were treated with IMRT-Shih, and 83 were treated with IMRT-RTOG. There were no acute grade 3 GI toxicities. Patients in the 4FB group had higher rates of acute grade ≥ 2 proctitis compared to the IMRT-Shih and IMRT-RTOG groups (16.0% vs 2.0% vs 2.4%, p=0.0009). The 4FB group also had higher rates of grade ≥ 2 flatulence compared to the 2 other IMRT groups (17.0% vs 7.6% vs 0%, p<0.0001). With regards to acute GU toxicities, patients in the 4FB group had higher rates of grade ≥ 3 urinary frequency compared to the 2 other IMRT groups (5.3% vs 0% vs 0%, p=0.027). Conclusions: In this non-randomized comparison, IMRT resulted in statistically significant decreases in acute proctitis, flatulence, and urinary frequency when compared to a 4FB technique to deliver EPNI in localized high risk prostate cancer. Analysis for possible confounding factors will be performed.

Treatment of HIV positive anal cancer patients with chemoradiation

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4154-4154
Author(s):  
J. M. Hwang ◽  
A. Rao ◽  
E. Shieh ◽  
J. Yao ◽  
M. Tome
Keyword(s):  
Cancer Patients ◽  
Mitomycin C ◽  
Anal Cancer ◽  
Negative Impact ◽  
Skin Toxicity ◽  
Distant Metastases ◽  
Complete Response ◽  
Suboptimal Control ◽  
Alive With Disease ◽  
Grade 3

4154 Background: Tolerance and outcomes of HIV+ anal cancer patients are questioned, especially since the emergence of High Active Anti-Retroviral Therapy (HAART) in the mid-1990s. Our experience in treating these patients before and during the HAART era is reported. Methods: From 1987–2003, 19 HIV+ invasive anal cancer patients were treated with: 30–60 Gy pelvic RT (2 Gy/d) + Mitomycin C (10 mg/m2 bolus on d1) + 5-FU (1000 mg/m2/d, continuous infusion d1–4 and 28–31). Results: Mean CD-4 count at cancer diagnosis was 311, with 9 on HAART. Mean CD-4 count for HAART was 383 and 247 for non-HAART. Stage distribution: 1 T1, 9 T2, 9 T3, 18 N0, 1 N3. Mean f/u was 40 months. 79% had complete response after chemoRT. 4 had locally persistent disease. There was 1 loco-regional recurrence and 2 distant metastases. 79% of the cohort is colostomy-free. Median OS has not been reached. OS at 2 and 3 years were: 88%and 79%, with 10 Alive and NED, 1 Alive with disease, 3 Dead of disease, 5 Dead from intercurrent disease (all secondary to AIDS). 1.5 year DFS was 74%. Break and CD-4 count < 200 had a statistically significant negative impact on DFS, but not OS. HAART did not affect either factor. 11 had RT break for median of 17 days. There was no Grade 4 skin toxicity. All completed the 2nd 5-FU cycle: 7 had delay (median 7 days) and 3 had dose decrease. There were 6 hospitalizations: 5 neutropenic fevers and 1 perineal abscess rupture. WBC Toxicity: 6-Grade 3 and 2-Grade 4. Platelet Toxicity: 2-Grade 3. Heme toxicity was not affected by HAART or CD4 count < 200. There were no treatment related deaths. Conclusion: HIV+ anal cancer patients have reasonable tolerance and outcomes with chemoRT. CD-4 count < 200 and break were negative prognostic factors for DFS. Our 79% colostomy free survival is similar to RTOG 9208, where suboptimal control was attributed to mandatory RT break. Factors influencing break include heme and skin toxicity. To improve the therapeutic ratio, substitution of Mitomycin-C with Cisplatin, IMRT, and Ethyol are being explored. No significant financial relationships to disclose.

Patterns of failure after adjuvant stereotactic body radiation therapy in patients with pancreatic cancer with close or positive margins.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 755-755
Author(s):  
Ankur Patel ◽  
Joshua L. Rodríguez-López ◽  
Nathan Bahary ◽  
Amer H. Zureikat ◽  
Steven A. Burton ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Target Volume ◽  
Patterns Of Failure ◽  
Positive Margins ◽  
Stereotactic Body Radiation ◽  
Kaplan Meier ◽  
Conventional Radiation ◽  
Target Volumes ◽  
Hypofractionated Radiation

755 Background: There is no consensus on treatment volumes for stereotactic body radiation (SBRT) in patients with pancreatic cancer (PCa). Herein, we report patterns of failure following adjuvant SBRT for close/positive margins in patients with pancreatic cancer, which may inform appropriate target volume design for SBRT. Methods: An IRB-approved retrospective review of patients with PCa treated with adjuvant SBRT for close/positive margins from 2009-2018 was conducted. Patterns of failure were assessed by review of imaging and were defined as local (LF), regional (RF), local and regional (LRF), or distant (DF). The Kaplan-Meier method was used to calculate long-term failure rates. In-field failures were defined as LFs completely within the PTV (planning target volume). The location of LFs was compared to the RTOG consensus volumes for adjuvant treatment of PCa to determine if conventional radiation volumes would have included the LF. Results: Seventy-six patients were treated with adjuvant SBRT for close (51.3%) or positive (48.7%) margins, with a median follow-up of 17.0 months (interquartile range [IQR] 7.4-28.3 mos.). Adjuvant SBRT was delivered at a median of 2.2 months after surgery (IQR 1.7-3.0 mos.). Most patients (81.6%) received 36 Gy in 3 fractions. The median PTV volume was 17.8 cc (IQR 12.3-25.2 cc). Upon examination of first failure sites, crude rates of isolated LF, isolated RF, isolated LRF, and DF +/- LF or RF were 9.2%, 6.6%, 2.6%, and 56.6% respectively; 2-year rates were 12.4%, 11.5%, 7.0%, and 66.5%, respectively. Thirty-two patients (42.1%) developed a LF at some point during follow-up. Of 28 LFs with available plans and imaging, 21.4% were in-field failures, while the remainder were completely outside (60.1%) or partially outside (17.9%) the PTV. Most LFs outside the PTV (90.9%) would have been encompassed by the RTOG consensus target volumes for postoperative conventional radiation. Conclusions: In patients with PCa who receive adjuvant SBRT for close/positive margins, the majority of LFs are outside the PTV. Future trials involving SBRT or hypofractionated radiation should consider expansion of treatment volumes if feasible.

ACUTE TOXICITY DUE TO RADIOTHERAPY IN ANAL CANAL CANCER PATIENTS

2011 ◽  
Vol 98 ◽  
pp. S35
Author(s):  
A. Alvarado ◽  
N. Feltes ◽  
J. Pardo ◽  
I. Modolell ◽  
J. Gonzalez ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Anal Canal ◽  
Cancer Patients ◽  
Anal Canal Cancer
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