Treatment Of Anal Canal Carcinoma Research Articles

Savremeni terapijski pristup u lečenju karcinoma analnog kanala

Savremeni terapijski pristup u lečenju karcinoma analnog kanala

Image Based Helical Tomotherapy With Concurrent Chemotherapy in the Treatment of Anal Canal Carcinoma: A Single-Institution Series

Image Based Helical Tomotherapy With Concurrent Chemotherapy in the Treatment of Anal Canal Carcinoma: A Single-Institution Series

Shifting paradigm in the management of anal canal carcinoma.

Anal canal is the lower most part of the gastrointestinal tract harbouring 4 % of all gastrointestinal cancer. Most common treatment for anal canal carcinoma includes chemoradiotherapy. We reviewed the recent landmark trials to find a road map in the management of anal canal carcinoma. Concurrent chemoradiotherapy appears to be the most effective treatment schedule. Induction, as well as maintenance chemotherapy, has no definite role. Moderate dose radiation 50.4-54 Gy with concurrent mitomycin C (MMC) and 5-fluorouracil (5-FU) remains the standard. Split course is detrimental. Intensity-modulated radiotherapy and targeted drugs are investigated. Combined modality therapy is the standard for anal canal carcinoma.

Radiation therapy of anal canal cancer: from conformal therapy to volumetric modulated arc therapy.

BackgroundTo appraise the role of volumetric modulated arc (RapidArc, RA) in the treatment of anal canal carcinoma (ACC).MethodsA retrospective analysis has been conducted on 36 patients treated with RA since 2009 comparing outcome against a group of 28 patients treated with conformal therapy (CRT). RA treatments were prescribed with SIB technique with 59.4 Gy to the primary tumor and nodes and 49.5 Gy to the elective nodes. CRT was sequentially delivered with 45 Gy to the pelvic target and a boost of 14.4 Gy to the primary tumor.ResultsMedian age of patients was 65 yrs for RA (59 yrs for CRT); 90% had Stage II-III (93% in the CRT group). No statistically significant differences were observed concerning survival or control. 5 yrs disease specific survival was 85.7% and 81.2%, loco-regional control was of 78.1% and 82.1% for RA and CRT respectively. RA treatments lead to lower incidence of higher grade of toxicity events (all retrospectively retrieved from charts as worse events). Grade 2–3 toxicity, compared to CRT, reduced from 89% to 68% for GI, from 39% to 33% for GU and from 82% to 75% for the skin. Late toxicity was as follows: 5/36 (14%) and 3/36 (8%) patients had G1 or G2 GI toxicity in the RA group (1/28 (4%) and 4/28 (14%) in the CRT group). GU late toxicity was observed only in 4/28 (14%) patients of the CRT group: 3/28 (11%) had G2 and 1/28 (4%) had G1.ConclusionsRA treatments of ACC patients proved to be equally effective than CRT but it was associated to a reduction of toxicity.

One compared with two cycles of mitomycin C in chemoradiotherapy for anal cancer: analysis of outcomes and toxicity.

Concurrent chemoradiation with fluorouracil (5fu) and mitomycin C (mmc) is standard treatment for anal canal carcinoma (acc). The current protocol in Alberta is administration of 5fu and mmc during weeks 1 and 5 of radiation. However, administration of the second bolus of mmc has been based largely on centre preference. Given limited published data on outcomes with different mmc regimens, our objective was to compare the efficacy and toxicity of 1 compared with 2 cycles of mmc in acc treatment. Our retrospective study evaluated 169 acc patients treated with radical chemoradiotherapy between 2000 and 2010 at two tertiary cancer centres. All patients were treated with 2 cycles of 5fu and with 1 cycle (mmc1) or 2 cycles (mmc2) of mmc. Acute toxicities, disease-free (dfs) and overall survival (os) were analyzed. Baseline demographics, performance status, and stage were similar in the groups of patients who received mmc1 (52%) and mmc2 (48%). Before treatment, median hematologic parameters were comparable, except for white blood cell count, which was higher in the mmc2 group, but within normal range. The 5-year os and dfs were similar (75.1% and 54.2% for mmc1 vs. 70.7% and 44.2% for mmc2, p = 0.98 and p = 0.63 respectively). On multivariate analysis, mmc2 was the factor most strongly associated with specific acute toxicities: grade 3+ leukopenia (hazard ratio: 4.82; p < 0.01), grade 3+ skin toxicity (hazard ratio: 4.76; p < 0.001), and hospitalizations secondary to febrile neutropenia (hazard ratio: 9.91; p = 0.001). In definitive chemoradiotherapy for acc, 1 cycle of mmc appears to offer outcomes similar to those achieved with 2 cycles, with significantly less acute toxicity.

Management of persistent anal canal carcinoma after combined-modality therapy: a clinical review

Anal canal carcinoma is a rare gastro-intestinal cancer. Radiochemotherapy is the recommended primary treatment for patients with non-metastatic carcinoma; surgery is generally reserved for persistent or recurrent disease. Follow-up and surveillance after primary treatment is paramount to classify patients in those with complete remission, persistent or progressive disease. Locally persistent disease represents a clinically significant problem and its management remains subject of some controversy.The aim of this systematic review is to summarise recommendations for the primary treatment of anal canal carcinoma, to focus on the optimal time to consider residual disease as genuine persistence to proceed with salvage treatment, and to discern how this analysis might inform future clinical trials in management in this class of patients.

Helical tomotherapy with concurrent chemotherapy in the treatment of anal canal carcinoma: A review of clinical outcomes at a tertiary referral center.

656 Background: We report the clinical outcomes of patients with anal carcinoma treated with helical tomotherapy (HT) IMRT and concurrent chemotherapy. Methods: From September 2005 to January 2013, 32 patients with squamous cell carcinoma of the anal canal received chemoradiation with HT planned in a consistent manner in parallel to the RTOG 0529 guidelines. Of the patients, 17 (53%) were T1-2, 13 (41%) were T3-T4, 15 (47%) were node positive, and 1 was M1 with para-aortic nodal metastases. There were 7 HIV positive and 3 renal transplant patients. All but 2 patients received 5-fluorouracil and mitomycin C. The median doses to the primary site, involved nodes, and uninvolved nodes were 54 Gy, 50.4 Gy, and 45 Gy, respectively. All acute and late toxicities were scored with the CTCAE v4.0. Results: Median follow-up was 31 months (range 10-97 months). Median length of treatment was 43 days. Twenty-two patients (69%) took a median of 3.5 break days. Acute grade 3-4 hematologic toxicity occurred in 27 patients (84%). There were no grade 4 gastrointestinal or dermatologic toxicities. Eight patients (25%) experienced grade 3 gastrointestinal and dermatologic toxicities. Twenty-one patients (66%) were hospitalized a total of 37 times during chemoradiation or within 90 days of therapy completion. Neutropenic fever was the most common reason for hospitalization, accounting for 30% of admissions. Thirty-one patients were followed for late toxicity with results as follows: 7 patients (23%) had grade 3 gastrointestinal toxicity, 1 patient (3%) had grade 3 dermatologic toxicity, and 3 patients (10%) had grade 3 sexual dysfunction. Nine patients (29%) developed pelvic insufficiency fractures, 5 requiring intervention. The 2-year progression-free and overall survivals were 97% and 97%, respectively. Two patients died; 1 from local progression and 1 from unrelated causes. Conclusions: HT delivering moderate radiation doses consistent with the RTOG 0529 guidelines and chemotherapy paired with aggressive, multidisciplinary management of acute and late toxicities effectively treat squamous cell carcinoma of the anal canal.

EP-1250: Clinical impact of tomoEDGE in the treatment of anal canal carcinoma

EP-1250: Clinical impact of tomoEDGE in the treatment of anal canal carcinoma

One Versus 2 Cycles of Mitomycin C in Concurrent Chemoradiation for Treatment of Anal Canal Carcinoma: An Analysis of Outcomes and Toxicity

Concurrent chemoradiation (CRT) with fluorouracil (5-FU) and mitomycin C (MMC) is widely accepted as the preferred definitive treatment in anal canal carcinoma (ACC). The current treatment protocol in Alberta has been administration of MMC followed by infusional 5-FU during weeks 1 and 5 of radiation. Administration of the second bolus of MMC, however, has been based largely on center preference. Given limited published data comparing outcomes for various MMC regimens, our objective was to compare efficacy and toxicity of 1 vs 2 cycles of MMC in ACC treatment.

Conformal external beam radiotherapy in the treatment of anal canal carcinoma: A retrospective study of a genital organ sparing technique

To investigate and compare the dosimetric distribution of a conventional radiotherapy (CRT) technique and a genital organ sparing three-dimensional conformal radiotherapy (3DCRT) technique for the treatment of anal canal cancer. Twenty-four patients with anal canal cancer treated between January 2002 and December 2006 were investigated. Each patient was retrospectively planned with the CRT and 3DCRT techniques using the Eclipse planning system (version 7.3, Varian Medical Systems, Palo Alto, CA, USA). Planning target volumes (PTVs) and surrounding organs at risk were contoured. Organs at risk included the bladder, bowel, femoral head and neck, and external genitalia. The two planning approaches were compared using dose volume histograms. Dose volume histograms of the PTV pelvis and PTV inguinal showed comparable PTV coverage between the two techniques. The mean percentage volumes of the PTV pelvis and PTV inguinal receiving at least 95% of the prescribed dose was greater than 99% and 91.5%, respectively. Dose volume histograms of the external genitalia demonstrated that they were well spared by the 3DCRT technique with mean doses of 28.30 and 13.17 Gy for the CRT and 3DCRT techniques, respectively. The percentage volume of bowel and bladder receiving 35 Gy or less was reduced with the 3DCRT technique. The femoral head and neck doses were comparable between the two techniques, with average maximum doses recorded of 40.60 and 40.69 Gy. The results of this study demonstrate that the 3DCRT technique achieves significant sparing of surrounding organs at risk, particularly the external genitalia. This organ at risk sparing was accomplished while achieving comparable PTV coverage with a CRT technique.

Anal Cancer: The End of the Road for Neoadjuvant Chemoradiotherapy?

Anal Cancer: The End of the Road for Neoadjuvant Chemoradiotherapy?

External beam radiotherapy and interstitial brachytherapy, with or without chemotherapy in the conservative treatment of anal canal carcinoma

External beam radiotherapy and interstitial brachytherapy, with or without chemotherapy in the conservative treatment of anal canal carcinoma

External beam radiotherapy plus brachytherapy boost in treatment of anal canal carcinoma

Radiotherapy has been the standard treatment of anal canal carcinoma for the last three decades. However, there are still many open questions such as optimal radiation technique, adequate boost dose or best chemotherapy regimen. Beside cure and local control, other important goals are sphincter salvage and avoidance of a permanent colostomy, i.e. morbidity minimization. At the Institute for Oncology and Radiology of Serbia, between March 1997 and May 2004, patients with anal canal carcinoma were treated with combined external beam radiotherapy and brachytherapy boost as primary treatment modality. Initially, external beam radiotherapy was applied with two opposed parallel fields and dose ranged from 40-50 Gy and after that patient continued the treatment with brachytherapy boost (intraluminal or interstitial) with doses ranged from 10-25 Gy. Total tumor dose in combined radiotherapy treatment ranged from 55-70 Gy. Out of 21 patients, acute complications were registered in 15 patients (71.4%) and the most frequent was dermatitis. Complete response after radiotherapy was registered in 17 patients (81%). In the median follow up time of 42 months, five-year overall survival was 71% and disease free survival was 61%. Late sequelas were registered in 14 patients (66.7%), but they were low grade. Our study shows results using external beam radiotherapy and brachytherapy boost as single modality treatment, but we need more randomized trial to improve better local control and minimize toxicity.

Radiochemotherapy in the conservative treatment of anal canal carcinoma: Retrospective analysis of results and radiation dose effectiveness

This retrospective analysis reports the results on patients with anal canal carcinoma treated by combined radiotherapy and chemotherapy. Between March 1993 and December 2001, 43 patients with anal canal carcinoma were treated with radiochemotherapy at the Hospital do Cancer A.C. Camargo. Stage distribution was as follows: I, 3 (7%); II, 23 (53.5%); IIIA, 8 (18.6%); and IIIB, 9 (21%). The median age was 56 years (range, 36-77 years) with most patients being women (4:1). External radiotherapy (RT) was delivered at the whole pelvis followed by a boost at the primary tumor. The median dose of RT at the whole pelvis and at the primary tumor was 45 Gy and 55 Gy, respectively. Chemotherapy was carried out during the first and last 4 days of RT with continuous infusion of 5-fluorouracil (1000 mg/m(2)) and bolus mitomycin C (10 mg/m(2)). Median overall treatment time was 51 days (range, 30-129 days). Thirty-four patients (79%) did not receive elective RT at the inguinal region. Patient's age, tumor stage, overall treatment time, and RT dose at primary tumor were variables analyzed for survival and local control. Median follow-up time was 42 months (range, 4-116 months). Overall survival and colostomy-free survival at 5 years was 68% and 52%, respectively. Overall survival according to clinical stage was as follows: I, 100%; II, 82%; IIIA, 73%; and IIIB, 18% (p = 0.0049). Complete response was observed in 40 patients (93%). Local recurrence occurred in 9 (21%) patients, and of these, 6 were rescued by surgery. Local control with a preserved sphincter was observed in 34 patients (79%). According to the RT dose, local control was higher among patients who received more than 50 Gy at primary tumor (86.5% vs. 34%, p = 0.012). Inguinal failure was observed in 5 patients (15%) who did not receive inguinal elective RT. Distant metastasis was observed in 11 patients (25.6%). Temporary interruption of the treatment as a result of acute toxicity was necessary in 12 patients (28%). Four patients developed mild chronic complications. This analysis suggests that the treatment scheme employed was effective for anal sphincter preservation and local control; however, the incidence of distant metastases was relatively high. The clinical stage was the main prognostic factor for overall survival. Local control was higher in patients treated with doses of more than 50 Gy at primary tumor. The high incidence of inguinal failure implies the need for elective RT in this region.

613 poster Conservative treatment of anal canal carcinoma: retrospective study

613 poster Conservative treatment of anal canal carcinoma: retrospective study

244 The conservative treatment of anal canal carcinoma

244 The conservative treatment of anal canal carcinoma

Contribution of conformal therapy in the treatment of anal canal carcinoma with combined chemotherapy and radiotherapy: results of a Phase II study

Purpose To evaluate the feasibility of delivering conformal radiotherapy (RT) and concurrent chemotherapy without a mandatory break in patients with anal canal carcinoma. Methods and materials Thirty patients with T2–T4 tumors were treated with a combination of 54 Gy in 30 fractions and two cycles of 5-fluorouracil and mitomycin C. Dose–volume histograms were obtained for bone marrow, small bowel, and skin to compare the conventional technique using the Radiation Therapy Oncology Group standard with our conformal technique. Results The mean dose ratio of the conventional compared with the conformal technique for bone marrow, small bowel, and skin was, respectively, 2.1–2.7, 3.0, and 2.0, in favor of the conformal technique. All patients completed their treatment without a treatment break. An incidence of Grade 3 toxicity for bone marrow, bowel, and skin of 13.3%, 3.3%, and 20%, respectively, was observed. With a median follow-up of 33 months, a 4-year local recurrence-free survival rate of 91% was observed. Conclusion The results of this study have shown that conformal RT leads to a well-tolerated treatment. The treatment time is shortened to 6 weeks. A significant decrease in the acute toxicity rate suggests that by decreasing the “volume factor,” conformal RT improves the therapeutic index in patients treated with combined chemotherapy and RT.

Radiotherapy (± chemotherapy) in the curative treatment of anal canal carcinoma (ACC). Lyon experience in 252 patients (pts)

Radiotherapy (± chemotherapy) in the curative treatment of anal canal carcinoma (ACC). Lyon experience in 252 patients (pts)

Squamous cell carcinoma of the anal canal

Purpose: To report the results of primary radiotherapy for treatment of anal canal carcinoma from the University of Florida series and review issues related to treatment of this disease. Methods and Materials: Forty-nine patients were treated with primary radiation therapy (RT) for cure. Patients had a minimum 2-year follow-up (median, 9.8 years). After 1990, patients with lesions of at least 3 cm also received chemotherapy with fluorouracil (1000 mg/m 2) plus cisplatin (100 mg/m 2) or mitomycin (10–15 mg/m 2) if medically fit ( n = 26). RT was delivered with a 4-field box technique to deliver 45 Gy in 25 fractions. The inguinal nodes were treated daily using electrons to supplement the dose in that region to a total dose of 45 Gy if clinically negative or about 60 Gy if involved. There were no planned breaks. A 10- to 15-Gy boost was delivered using interstitial iridium 192 implant ( n = 32), en face 60Co field ( n = 5), or external-beam photon fields ( n = 11). Results: Local control rates at 5 years were 100% for T1N0, 92% for T2N0 or N1, 75% for T3N0, 67% for T4N0, 88% for T4N pos or T anyN2–3, and 85% overall. With surgical salvage, ultimate local control rates were 100%, 100%, 81%, 100%, and 88%, respectively, with 92% overall. Cause-specific survival rates at 5 years were 100% for Stage I, 88% for Stage II, 100% for Stage IIIA, and 70% for Stage IIIB. Absolute survival rates at 5 years were 62%, 68%, 100%, and 70%. Sphincter preservation rates were 83%, 79%, 75%, and 100% by stage and 81% overall. There was an improvement in local control with the addition of chemotherapy in more advanced disease, but it was not significant. There was an increase in acute toxicity with the addition of chemotherapy (12% ≥ Grade 4) but not long-term toxicity. Late toxicity requiring colostomy occurred in 6% of patients and consisted of soft tissue necrosis. Conclusions: The majority of patients with anal canal carcinoma can be treated with curative intent using a sphincter-sparing approach of radiation with or without chemotherapy even with advanced disease. With the addition of chemotherapy to radiation, there is an increased risk of acute toxicity and about 1–2% incidence of toxic death. Smaller tumors (T1 and early T2) probably do not require the addition of chemotherapy.

26 Radiotherapy (±Chemotherapy) in the curative treatment of anal canal carcinoma (ACC). Lyon experience in 252 patients

26 Radiotherapy (±Chemotherapy) in the curative treatment of anal canal carcinoma (ACC). Lyon experience in 252 patients