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Title: Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer

Abstract

Purpose: Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer. Methods and Materials: A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction. Results: During phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively. Conclusion: Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery.

Authors:
 [1];  [1];  [1];  [2];  [3];  [4]; ; ; ; ;  [1]; ;  [5];  [6];  [7];  [8];  [5]
  1. Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)
  2. (United States)
  3. Ion Beam Therapy Center, SAGA HIMAT Foundation, Saga (Japan)
  4. Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan)
  5. Graduate School of Medicine, Chiba University, Chiba (Japan)
  6. Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome, Tokyo (Japan)
  7. National Hospital Organization Osaka National Hospital, Osaka (Japan)
  8. National Cancer Center Hospital East, Kashiwa, Chiba (Japan)
Publication Date:
OSTI Identifier:
22648785
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 96; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ABSORBED RADIATION DOSES; CARBON IONS; GY RANGE 01-10; GY RANGE 10-100; NEOPLASMS; PATIENTS; RADIOTHERAPY; RBE; RECTUM

Citation Formats

Yamada, Shigeru, E-mail: s_yamada@nirs.go.jp, Kamada, Tadashi, Ebner, Daniel K., Brown University Alpert Medical School, Providence, Rhode Island, Shinoto, Makoto, Terashima, Kotaro, Isozaki, Yuka, Yasuda, Shigeo, Makishima, Hirokazu, Tsuji, Hiroshi, Tsujii, Hirohiko, Isozaki, Tetsuro, Endo, Satoshi, Takahashi, Keiichi, Sekimoto, Mitsugu, Saito, Norio, and Matsubara, Hisahiro. Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.04.022.
Yamada, Shigeru, E-mail: s_yamada@nirs.go.jp, Kamada, Tadashi, Ebner, Daniel K., Brown University Alpert Medical School, Providence, Rhode Island, Shinoto, Makoto, Terashima, Kotaro, Isozaki, Yuka, Yasuda, Shigeo, Makishima, Hirokazu, Tsuji, Hiroshi, Tsujii, Hirohiko, Isozaki, Tetsuro, Endo, Satoshi, Takahashi, Keiichi, Sekimoto, Mitsugu, Saito, Norio, & Matsubara, Hisahiro. Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer. United States. doi:10.1016/J.IJROBP.2016.04.022.
Yamada, Shigeru, E-mail: s_yamada@nirs.go.jp, Kamada, Tadashi, Ebner, Daniel K., Brown University Alpert Medical School, Providence, Rhode Island, Shinoto, Makoto, Terashima, Kotaro, Isozaki, Yuka, Yasuda, Shigeo, Makishima, Hirokazu, Tsuji, Hiroshi, Tsujii, Hirohiko, Isozaki, Tetsuro, Endo, Satoshi, Takahashi, Keiichi, Sekimoto, Mitsugu, Saito, Norio, and Matsubara, Hisahiro. 2016. "Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer". United States. doi:10.1016/J.IJROBP.2016.04.022.
@article{osti_22648785,
title = {Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer},
author = {Yamada, Shigeru, E-mail: s_yamada@nirs.go.jp and Kamada, Tadashi and Ebner, Daniel K. and Brown University Alpert Medical School, Providence, Rhode Island and Shinoto, Makoto and Terashima, Kotaro and Isozaki, Yuka and Yasuda, Shigeo and Makishima, Hirokazu and Tsuji, Hiroshi and Tsujii, Hirohiko and Isozaki, Tetsuro and Endo, Satoshi and Takahashi, Keiichi and Sekimoto, Mitsugu and Saito, Norio and Matsubara, Hisahiro},
abstractNote = {Purpose: Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer. Methods and Materials: A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction. Results: During phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively. Conclusion: Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery.},
doi = {10.1016/J.IJROBP.2016.04.022},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 96,
place = {United States},
year = 2016,
month = 9
}
  • Purpose: Although vaginal stenosis (VS) is a recognized toxicity in women who receive pelvic radiation therapy (RT), the relationship between RT dose and the volume and extent of toxicity has not been analyzed. We modeled this relationship to identify predictors of VS. Methods and Materials: We evaluated 54 women, aged 29 to 78 years, who underwent pelvic RT for rectal or anal cancer during 2008 to 2011 and were enrolled in a prospective study evaluating vaginal dilator use. Maximum dilator size was measured before RT (baseline) and 1 month and 12 months after RT. Dilator use was initiated at 1 month. The difference (D)more » in dilator size before and after RT was recorded. Those with D ≤−1 were classified as having VS (n=35); those with D ≥0 were classified as having no VS (n=19 at 1 month). Dose-volume parameters were extracted, and the generalized equivalent uniform dose (gEUD) was used to build a predictive model. Results: The mean vaginal doses were 50.0 Gy and 36.8 Gy for anal and rectal cancer patients, respectively. One month after RT, a gEUD model using a wide range of a values suggests that sparing of vaginal volume to a low dose may be important. When gEUD (a = −1) was <35 Gy and the mean vaginal dose was <43 Gy, severe VS was reduced (P=.02). A 1-year analysis suggests increasingly negative D values with increasing mean dose. However, patients with compliance <40% were more likely to have toxicity. Conclusions: Vaginal stenosis is influenced by multiple RT dose-volume characteristics. Mean dose and gEUD constraints together may reduce the risk of severe VS. Patients receiving higher mean vaginal doses should have greater compliance with dilator therapy to minimize risk of toxicity. Further validation with independent datasets is needed.« less
  • Purpose: To assess the efficacy of robotic-assisted laparoscopic sentinel lymph node (SLN) dissection (SLND) to select those patients with prostate cancer (PCa) who would benefit from additional pelvic external beam radiation therapy and long-term androgen deprivation therapy (ADT). Methods and Materials: Radioisotope-guided SLND was performed in 224 clinically node-negative patients scheduled to undergo external beam radiation therapy. Patients with histologically positive SLNs (pN1) were also offered radiation therapy to the pelvic lymph nodes, combined with 3 years of ADT. Biochemical recurrence (BCR), overall survival, and metastasis-free (including pelvic and nonregional lymph nodes) survival (MFS) rates were retrospectively calculated. The Briganti andmore » Kattan nomogram predictions were compared with the observed pN status and BCR. Results: The median prostate-specific antigen (PSA) value was 15.4 ng/mL (interquartile range [IQR] 8-29). A total number of 834 SLNs (median 3 per patient; IQR 2-5) were removed. Nodal metastases were diagnosed in 42% of the patients, with 150 SLNs affected (median 1; IQR 1-2). The 5-year BCR-free and MFS rates for pN0 patients were 67.9% and 87.8%, respectively. The corresponding values for pN1 patients were 43% and 66.6%. The PSA level and number of removed SLNs were independent predictors of BCR and MFS, and pN status was an additional independent predictor of BCR. The 5-year overall survival rate was 97.6% and correlated only with pN status. The predictive accuracy of the Briganti nomogram was 0.665. Patients in the higher quartiles of Kattan nomogram prediction of BCR had better than expected outcomes. The complication rate from SLND was 8.9%. Conclusions: For radioisotope-guided SLND, the high staging accuracy is accompanied by low morbidity. The better than expected outcomes observed in the lower quartiles of BCR prediction suggest a role for SLN biopsy as a potential selection tool for the addition of pelvic radiation therapy and ADT intensification in pN1 patients.« less
  • An unsolved problem in colon and rectal surgery involves the treatment of locally invasive primary and recurrent rectal cancer. An approach is described that uses intracavitary iridium-192 sources in combination with a pelvic displacement prosthesis to augment external beam radiation doses to sites of residual disease identified at surgery. This approach should permit administration of tumoricidal doses of radiation to positive surgical margins minimizing radiation toxicity to the small bowel. The radiation source and all prosthetic materials are removed at the bedside within 2 weeks of surgery, ensuring accurate radiation dosimetry, minimizing infectious complications, and sparing the patient the needmore » for full high-dose pelvic irradiation.« less
  • The acute and delayed complications of pelvic radiation therapy for rectal cancer occur with distinct clinical courses and pathological manifestations. Acute complications are common during treatment, are usually transient, and resolve within a few weeks following the completion of radiation. Delayed complications occur less frequently but are substantially more serious, with the most common being small bowel damage. With the use of more sophisticated radiation techniques, methods to exclude the small bowel from the pelvis during radiotherapy, and possibly elemental diets, the toxicity can be minimized.
  • Purpose: To perform a prospective phase II study to investigate the efficacy and safety of preoperative pelvic radiation therapy and concomitant small-field boost irradiation with 5-fluorouracil and leucovorin for 5 weeks in locally advanced rectal cancer patients. Methods and Materials: Sixty-nine patients with locally advanced, nonmetastatic, mid-to-lower rectal cancer were prospectively enrolled. They had received preoperative chemoradiation therapy and total mesorectal excision. Pelvic radiation therapy of 43.2 Gy in 24 fractions plus concomitant boost radiation therapy of 7.2 Gy in 12 fractions was delivered to the pelvis and tumor bed for 5 weeks. Two cycles of 5-fluorouracil and leucovorin weremore » administered for 3 days in the first and fifth week of radiation therapy. The pathologic response, survival outcome, and treatment toxicity were evaluated for the study endpoints. Results: Of 69 patients, 8 (11.6%) had a pathologically complete response. Downstaging rates were 40.5% for T classification and 68.1% for N classification. At the median follow-up of 69 months, 36 patients have been followed up for more than 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 66.0% and 75.3%, respectively. Higher pathologic T (P = .045) and N (P = .032) classification were significant adverse prognostic factors for DFS, and high-grade histology was an adverse prognostic factor for both DFS (P = .025) and overall survival (P = .031) on the multivariate analysis. Fifteen patients (21.7%) experienced grade 3 or 4 acute toxicity, and 7 patients (10.1%) had long-term toxicity. Conclusion: Preoperative pelvic radiation therapy with concomitant boost irradiation with 5-fluorouracil and leucovorin for 5 weeks showed acceptable acute and long-term toxicities. However, the benefit of concomitant small-field boost irradiation for 5 weeks in rectal cancer patients was not demonstrated beyond conventional irradiation for 6 weeks in terms of tumor response and survival.« less