Radiation Therapy For Anal Cancer Research Articles

Evaluation of Planned Treatment Breaks During Radiation Therapy for Anal Cancer: Update of RTOG 92-08

Radiation Therapy Oncology Group (RTOG) 92-08 began as a single arm, Phase II trial for patients with anal cancer consisting of radiation (RT) + 5-flourouracil + mitomycin-C with a mandatory 2-week break and was amended after completion to evaluate the same treatment regimen without a treatment break. Long-term efficacy and late toxicity reporting are the specific aims of this study. Survivals were estimated with the Kaplan-Meier method. Overall survival (OS) was compared with RTOG 87-04 with the log-rank test. Time to local failure, regional failure, locoregional failure (LRF), distant metastases, second primary, and colostomy failure were estimated by the cumulative incidence method. LRF was compared with RTOG 87-04 using the Gray's test. Forty-seven patients entered in the mandatory treatment break cohort. The study was reopened in 1995 to the no mandatory treatment break cohort completing accrual with 20 patients in 1996. Of 67 total patients, 1 patient in the mandatory treatment break portion of the study did not receive any protocol treatment and is excluded from analyses. After adjusting for tumor size, neither cohort showed a statistically significant difference in OS or LRF compared with the RTOG 87-04 mitomycin-C arm. No patient in either cohort experienced a Grade 3 or higher late toxicity. No statistically significant differences were seen in OS or LRF when compared to the mitomycin-C arm of RTOG 87-04, but the sample sizes for the mandatory break cohort and the no mandatory break cohort are small. Late toxicity was low and similar for the treatment cohorts.

Potential and Limitations of Intensity-Modulated Radiotherapy in Anal Cancer

Potential and Limitations of Intensity-Modulated Radiotherapy in Anal Cancer

Perineal Skin Toxicity according to Irradiation Technique in Radiotherapy of Anal Cancer

Perineal Skin Toxicity according to Irradiation Technique in Radiotherapy of Anal Cancer

Current treatment for localized anal carcinoma

Chemoradiation represents the standard of care for most patients with localized squamous cell carcinoma of the anal canal. This article reviews randomized trials and recent studies on chemoradiation for anal cancer. A recent randomized trial showed that patients treated with induction 5-fluorouracil/cisplatin followed by concurrent 5-fluorouracil/cisplatin and radiotherapy had a higher colostomy rate than patients treated with concurrent 5-fluorouracil/mitomycin C and radiotherapy. It remains unclear whether this difference in the rate of colostomy was due to the chemotherapy agents, the use of induction therapy in the 5-fluorouracil/cisplatin arm, or other factors. Recent studies have started to evaluate intensity modulated radiation therapy for anal cancer, in an effort to reduce acute and long-term toxicity from radiotherapy. The role of cisplatin in anal cancer is not completely clear, although an ongoing randomized trial (Anal Cancer Trial II) may help clarify the role of cisplatin. Studies on tumor biology and patient genetics are warranted to identify patients that are most likely to benefit from newer locoregional and systemic therapies. Intensity modulated radiation therapy appears to be a promising approach for reducing treatment-related toxicity in anal cancer patients. The Radiation Therapy Oncology Group (RTOG) is conducting a phase II trial evaluating the multi-institutional feasibility of intensity modulated radiation therapy for anal cancer.

High Risk of Colostomy with Primary Radiotherapy for Anal Cancer

Radiotherapy (RT) has become the primary treatment of choice for anal cancer in an effort to avoid colostomy. The current role of surgery appears generally to be underestimated, since diverting colostomy or abdominoperineal resection still often seems to be necessary for complications and local treatment failure after RT. The data of 83 patients primarily treated by RT with curative intent throughout a 20-year period in our institute were analyzed regarding the need for colostomy. Totally, 28 patients (34%) required creation of a colostomy after primary RT for local failure or treatment-related complications during a mean follow-up period of 39 months. The 3-year actuarial colostomy-free rate was 59% (mean 85 +/- 9 months). Early stage disease, low T-score and absence of infiltration in adjacent organs were associated with a reduced need for colostomy in univariate analysis. In multivariate analysis only T-score was an independent variable in predicting prolonged colostomy-free interval. In this study, no statistically significant differences were noted for gender, age, nodal status, total radiation dose, radiation boost and concurrent chemotherapy. In approximately one-third of the patients treated by anal sphincter saving management with curative aimed primary RT, the creation of a colostomy appeared to be necessary for RT complications and local treatment failure. Therefore, patients should be well informed regarding the considerable risk of need for colostomy after RT for anal cancer.

2126: Dose-Painted Intensity Modulated Radiation Therapy for Anal Cancer: Dosimetric Comparison and Acute Toxicity

Radiation therapy (RT) with concurrent 5-fluorouracil (5-FU) and mitomycin-C (MMC) is the standard treatment for anal cancer but results in significant grade 3/4 hematologic, dermatologic, and gastrointestinal (GI) morbidity. Intensity modulated RT (IMRT) reduces the volume of normal tissue exposed to high dose radiation and may reduce the toxicity of chemoradiation. IMRT for anal cancer has been described in a two-phase technique (large field and boost). However, no reports exist on the use of dose-painting techniques to produce full-course IMRT plans.

815 POSTER Androgen deprivation for cytoreduction prior to interstitial brachytherapy for early-stage prostate cancer is associated with an increased risk of urinary morbidity

Anal cancer patients treated with radiation therapy (RT) have an increased risk of hip fractures after treatment. The mechanism of these fractures is unknown; however, femoral fractures have been correlated with cortical bone thinning. The objective of this study was to assess early changes in cortical bone thickness at common sites of femoral fracture in anal cancer patients treated with intensity modulated radiation therapy (IMRT).RT treatment plans and computed tomography (CT) scans from 23 anal cancer patients who underwent IMRT between November 2012 and December 2014 were retrospectively reviewed. Cortical thickness (Ct.Th) was mapped at homologous vertices within the proximal femur using pre-RT and post-RT (≤ 4 months) CT scans. The bone attenuation measurements were collected at homologous locations within the trabecular bone of the right femoral neck (FN). The percent change in Ct.Th and trabecular bone mineral density (trBMD) were assessed. FN cortical thinning was correlated to RT dose using linear regression. A logistic model for dose dependent cortical thinning was constructed.Twenty-two patients were analyzed. Significant post-treatment cortical thinning was observed in the intertrochanteric crest, subcapital and inferior FN (p < 0.05). FN volume receiving ≥ 40 Gy (V40Gy) was a significant predictor of focal cortical thinning ≥ 30% (p = 0.03). A significant decrease in FN trBMD was observed (− 6.4% [range − 34.4 to 3.3%]; p = 0.01).Significant early decrease in Ct.Th and trBMD occurs at the FN in patients treated with RT for anal cancer. FN V40Gy was predictive of clinically significant focal FN cortical thinning.

Organ sparing by conformal avoidance intensity-modulated radiation therapy for anal cancer: Dosimetric evaluation of coverage of pelvis and inguinal/femoral nodes

To describe a novel and straightforward conformal avoidance intensity-modulated radiation therapy (IMRT) technique for coverage of pelvis and inguinal/femoral nodes and to compare the dosimetry of the new method with that of other traditional methods of radiation treatment. Data of 2 patients with anal cancer were used as example cases to illustrate details and advantages of conformal avoidance IMRT technique. Conventional photons with enface electrons design was created first, thereby providing "outermost boundaries" defined as planning target volume (PTV) for subsequent conformal avoidance IMRT design. Organs at risk (OARs), including femoral head and neck and external genitalia, were contoured as conformal avoidance structures. A step-and-shoot inverse IMRT planning was subsequently generated. For dosimetric comparison, a recently published technique by modified segmental boost was also generated. These treatment techniques were evaluated by dose-volume histogram (DVH) of PTV and OARs. Dose profiles at four different depths from each treatment planning were generated for comparison. The DVH of PTV showed that coverage of the PTV was comparable among three treatment techniques. Percent volume of PTV receiving more than 90% prescription dose was in the range 94-98% for the three treatment techniques, and all had only 0-2% of PTV receiving more than 110% of prescription dose. The DVH of OARs confirmed that both femoral head and neck and external genitalia could be spared well by conformal avoidance IMRT as compared with the other two techniques. Although greater inhomogeneity of dose distribution within the PTV was noted by conformal avoidance IMRT technique, as shown by dose profiles at four different depths, the maximum doses at different depths were less than 115%, which was comparable to those planned by modified segmental boost technique. Planning by photons and enface electrons technique, however, showed a greater dose variation up to 134% of the prescription dose at 1.5 cm depth along photon-electron match-line. To cover pelvis and inguinal/femoral nodes, conformal avoidance IMRT is technically simple to simulate, plan, and execute. Dosimetric study has demonstrated that it achieves comparable PTV coverage compared with other approaches while at the same time significantly sparing the surrounding OARs.

Organ sparing by conformal avoidance intensity modulated radiation therapy for anal cancer: Dosimetric evaluation of coverage of pelvis and inguinal/femoral nodes

4257 Background: To describe a novel and straightforward conformal avoidance IMRT technique for coverage of pelvis and inguinal/femoral nodes and to compare the dosimetry of the new method with that of other methods of radiation treatment. Methods: Data of 2 patients with anal cancer were used as example cases to illustrate details and advantages of conformal avoidance IMRT technique. Conventional photons with enface electrons design was created first, thereby providing “outermost boundaries” defined as planning target volume (PTV) for subsequent conformal avoidance IMRT design. Organs at risk (OARs) including femoral head and neck and external genitalia were contoured as conformal avoidance structures. A step-and-shoot inverse IMRT planning was generated. For dosimetric comparison, technique by modified segmental boost was also generated. These treatment techniques were evaluated by dose volume histogram (DVH) of PTV and OARs. Dose profiles at 4 different depths from each treatment planning were generated. Results: DVH of PTV shows that coverage of the PTV is comparable among 3 treatment techniques. Volume of PTV receiving more than 90% prescription dose are in the range of 94 to 98% for the 3 treatment techniques and all have only 0 to 2% of PTV receiving more than 110% prescription dose. DVH of OARs confirms that both femoral head and neck and external genitalia could be spared well by conformal avoidance IMRT. Although greater inhomogeneity of dose distribution within the PTV is noted by conformal avoidance IMRT as shown by dose profiles at 4 depths, the maximum doses at different depths are less than 115% which are comparable to the planning by modified segmental boost technique. Planning by photons and enface electrons technique however shows a greater dose variation up to 134% of the prescription dose at 1.5 cm depth along photon-electron match-line. Conclusions: To cover pelvis and inguinal/femoral nodes conformal avoidance IMRT is technically simple to simulate, plan and execute. Dosimetric study demonstrated that it achieves comparable PTV coverage compared with other approaches while at the same time significantly spares the surrounding OARs. No significant financial relationships to disclose.

Induction chemotherapy followed by radiotherapy in the treatment of anal cancer

This study was conducted to investigate the efficacy of the induction chemotherapy followed by radiotherapy in anal cancer. Twenty-three patients diagnosed with anal cancer between March 1991 and February 1999 were treated with induction chemotherapy with 5-fluorouracil based regimens followed by external beam radiation. After a median follow-up of 78 months, the overall survival and the disease-free survival at 5 years was 71.3 and 67.5%, respectively. The colostomy-free survival at 5 years was 91%, as the inguinal lymph nodes were the most frequent site of relapse. Serious side effects did not occur and late complications did not develop either. Induction chemotherapy followed by radiotherapy in patients with anal cancer is effective in terms of its response and preserving the anal sphincter without serious acute and late complications.

Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: Ten years experience

Purpose : To report our experience in the use of interstitial iridium-192 implantation combined with external radiotherapy in anal cancer. Methods and Matarials : From 1984 to 1994, 79 patients with anal cancer were treated with radical intent using radiotherapy (plus chemotherapy) at Beatson Oncology Centere, Glasgow, Scotland. The mean and median age at presetantion were 68 and 70 years, respectively (range 34–85) with a male-to-female ratio of 0.39. The histologic distribution was as follows: 48 squamous, 16 basaloid, 14 adenocarcinoma, and 1 basal cell carcinoma. The T stages were: 8 T1, 40 T2, 26 T3, and 5 T4 lesions. Twelve (15%) patients had nodal involvement at presentation. All patients underwent interstitial implantation using iridium-192 as part of the initial treatment. Seventy-six patients were treated with external radiotherapy followed by implant with a mean delay of 37 days after the end of radiotherapy. Twelve patients also received chemotherapy with 5-fluorouracil and mitomycin-C concurrently with external radiotherapy. Follow-up ranged from 6 to 123 months, and with median of 37 months. Results : Seventy-nine patients were analyzed to assess local control, survival, and complications. A complete response rate of 91% (72 of 79) was achieved after planned radiation treatment. At the end of external radiotherapy, 29% (22 of 76) had achieved complete response, 58% (7 of 12) with chemotherapy and 23% (15 of 64) without it. Local control was achieved in 62 of 79 (78%) patients and 8 of 17 (47%) local failures were salvage by abdominoperineal resection. Five patients developed inguinal node failure; four of these were salvaged. Overall, 10% of all patients developed distant metastasis as the first site of failure and 25% failed at any site after salvage therapy. Time to unsalvageable relapse was significantly different on comparing T stage ( p = 0.005) and histology ( p = 0.029) of tumor. Major requiring surgical intervention were seen in six (7.5%) patients. Anal function preservation with local control was possible in 56 of 79 (71%) patients. Conclusion : We report excellent results with radiotherapy in T1 and T2 lesions. The role of chemoradiotherapy as radical treatment of anal cancer should be defined in the context of locally andvanced tumors.

New method of radiotherapy for anal cancer with three-dimensional tumor reconstruction based on endoanal ultrasound and ultrasound-guided afterloading therapy.

Standard treatment of anal cancer is a protocol of combined chemotherapy and percutaneous radiotherapy. We developed a new endosonography-based radiation target simulation method, because endoanal sonography gives the best opportunity to stage the tumor accurately. Based on this method, an afterloading needle application procedure could be performed to optimize the radiation target geometry and to control the application of afterloading needles. In a prospective study, this new method was evaluated, with special regard for complications and tumor recurrence. Anal cancer was restaged endosonographically six weeks after external beam radiation with 45 Gy. A computer-generated three-dimensional reconstruction of the tumor and radiation target simulation was performed based on endoanal sonographic imaging. By using a new type of applicator, which is permeable to ultrasound waves, the transperineal implantation procedure of afterloading needles could be controlled. Application needles were inserted into the target area according to the endoanal sonography-based dosimetry planing. The dose of the (high-dose rate) brachytherapy boost was started with two 6-Gy fractions, each within eight days. The fraction dose was reduced to 4 Gy to minimize side effects. Lymph node-positive tumors got additional chemotherapy (5-fluorouracil and mitomycin C). From January 1992 until August 1996, we performed 42 endosonography-guided afterloading procedures in 18 patients. One patient underwent percutaneous radiation two years before and was treated only by afterloading radiation. In every patient, we found complete tumor remission at the end of radiotherapy. Three patients with a high-dose rate of 2 x 6 Gy developed radiogenic proctitis, and two patients developed ulceration, which lead to reduction of the dose. After reduction to 4 Gy per fraction, no more side effects could be seen. In follow-up (median, 24 (range, 1-56) months), we detected two anal cancer recurrences (2/18 patients). The radiation target field can be optimized by individual endosonography-based three-dimensional tumor reconstruction and radiotherapy simulation. Endosonography-guided transperineal implantation of afterloading needles can be performed according to the computer-generated simulation by using a new type of applicator. We could achieve total primary tumor remission in every patient. After reduction of the afterloading dose to 2 x 4 Gy, no brachytherapy-related side effects could be seen.

2036 Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: Ten years experience

2036 Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: Ten years experience

Radiation treatment of epidermoid cancer of the anus

Purpose : The purpose of this study was to evaluate our treatment results of anal cancer. Methods and Materials : During the years 1985–1990, 82 patients with invasive epidermoid anal cancer were referred to the Department of Oncology at Sd̈ersjukhuset. In 76 cases irradiation was used in the primary therapy, and in 43 cases bleomycin was administered concurrently. Fifteen of these tumors were situated in the perianus and 61 in the anal canal. Probability of survival, recurrence, and preservation of anal sphicter was analyzed according to Kaplan-Meier. Cox multivariate analysis was used in studying potential determinants of risk for treatment failure. Results : Tumor-specific survival at 5 years was 71% for both anal canal and perianal cancer. Analyses with regard to cancer of the anal canal indicated that T4 tumors had significantly worse prognosis than those in stages TI-3. Overall survival was 73% and 79% at 5 years for T1 and T2 tumors and 73% and 18% at 4 years for T3 and T4 tumors. Corresponding figures for tumor specific survival were 79%, 79%, 82%, and 31%. Eighty-five precent of patients with T1 tumors, has a preserved anal sphincter after 4 years. For T2 and T3 tumors the corresponding figures were 62% and 60%. Also the multivariate analyses showed t$ to be a strong negative prognostic determinant. There was no firm evidence of a positive effect of bleomycin on the treatment results, but it increased the acute radiation toxicity. Conclusion : Primary radiotherapy of anal cancer yielded a high probability of survival, but in many cases sphincter amputation have been necessary. The role of bleomycin appears questionable.

Combined chemotherapy—radiotherapy of anal cancer

Forty-five patients were treated from 1984 to 1988. Thirty-eight, with a minimum follow-up of 6 months, are considered evaluable: median age, 62 years (25–88); males 6, females 32; T1 = 7, T2 = 21, T3 = 10; inguinal positive nodes, 5 patients. Chemotherapy (CT) (Mitomycin C, 15 mg/sqm, bolus day 1; 5-FU, 750 mg/sqm, 24 hr infusion, days 1 to 5) and radiotherapy (RT) started the same day. A dose of 36 Gy was given to the tumor and to the pelvis including inguinal nodes, in 20 fractions. After 2 weeks a boost of RT (18 Gy) to the ano-perineal area and a second cycle of CT completed the treatment. CR (biopsy) was achieved in 32 38 patients (84.2%). Among the six patients on PR, four received a Miles operation (2 NED), and two a wide local resection (both NED). Five out of 32 CRs relapsed: 2 5 were rescued with a Miles resection, 3 died from progression. In conclusion, 32 38 patients (84.2%) are NED after a median follow-up of 22 months and 28 of them retained their anal sphincter. A longer follow-up is needed to define optimal treatment modality, but it is clear that surgery must play a minor role in the treatment of anal cancer.

Radiotherapy for anal cancer: Experience from 1979–1987

Seventy patients with squamous cell carcinoma or cloacogenic carcinoma of the anus treated from 1979–1987 were reviewed. Five groups were analyzed: (a) local excision (LE) with postoperative radiotherapy (n = 9); (b) abdomino-perineal resection (APR) with either pre- or postoperative radiotherapy (n = 22); (c) definitive radiotherapy alone (n = 8); (d) radiotherapy with continuous 5-Fluorouracil (5-FU) infusion (chemoradiation) (n = 25); and (e) patients treated for recurrent disease (n = 6). Abdomino-perineal resection and radiotherapy resulted in an actuarial local control (LC) rate of 90% and an overall 5-year survival rate of 77% (median follow-up, 48 months). All patients in Group 1 and 5 8 patients in Group 3 had locally controlled disease and were disease-free. The chemoradiation protocol resulted in a complete clinical response rate of 75% ( 18 24 , one patient died during treatment) assessed 4–6 weeks after treatment. The colostomy-free local control rate with chemoradiation is 67% ( 16 24 ). Local control was 50% for all stages receiving 45–49 Gy and 90% for those patients receiving ?55 Gy but was not correlated with total 5-FU dose. Abdomino-perineal resection was performed to salvage six patients with persistent disease and two with recurrent disease, resulting in an overall local control rate of 92% ( 22 24 ) . The actuarial survival was 96% (median follow-up, 14 months; range, 1–30). The acute complications of radiotherapy included diarrhea and perineal skin reactions that were increased by 5-FU infusion. However, diarrhea can be ameliorated by a modified treatment technique that reduces irradiation to the small intestine. For the entire patient group, minor late complications occurred in 23%, and major complications occurred in 9%.