George Kyrgias

Dose escalation of amifostine for radioprotection during pelvic accelerated radiotherapy.

Objectives: Experimental data suggest a dose-dependent efficacy of amifostine so that the low overall doses used in clinical trials may have masked the full potential of the drug. In this study, we report our experience with the role of escalated doses of amifostine in the protection of pelvic tissues. Methods: A total of 354 patients with pelvic carcinomas recruited in prospective protocols applying hypofractionated and accelerated radiotherapy (HypoARC) supported with escalated daily doses of amifostine (0, 500, 750, 1000 mg subcutaneously) were analyzed. Conformal pelvic radiation delivered 14 daily fractions of 2.7 Gy within 18 days, whereas booster techniques increased the daily fraction to the target area to 3.4 Gy. Results: Using a dose-individualization algorithm, 55.4% tolerated a daily amifostine dose of 1000 mg (level 3), 15.9% of 750 mg (level 2), and 17.5% of 500 mg (level 1), whereas intolerance induced amifostine interruption in 11.3% of the patients. Early grade 2/3 urinary frequency and dysuria grades 1 to 2 were significantly higher in level 0 patients (P=0.04 and 0.01, respectively). The dose level (1 to 3) of amifostine did not influence the incidence of frequency/dysurea. Acute diarrhea and proctitis grade 2/3 were significantly lower only in level 3 (P<0.0001 and 0.03, respectively). Dose level 3 was also linked to reduced incidence of late bladder and intestinal toxicities (P<0.05). Local control analysis showed no tumor protection effect of amifostine. Conclusions: Higher amifostine doses are tolerable by patients with pelvic malignancies and can better protect pelvic tissues against early and short-term late effects of radiotherapy.

Accelerated hypofractionated whole-breast irradiation with concomitant daily boost in early breast cancer.

Objectives:The aim of this study is to evaluate the feasibility and the related toxicity of hypofractionated whole-breast irradiation with a concomitant daily boost in early breast cancer women not eligible for accelerated partial-breast irradiation. Methods:Twenty-seven patients received 46 Gy to the whole breast in 20 fractions/4 weeks with 2.3 Gy/fraction plus an additional concomitant daily boost of 0.4 Gy to the tumor bed, giving a total dose of 54 Gy (EQD2=60 Gy). The cosmetic outcome was assessed according to the European Organization for Research and Treatment of Cancer and Radiation Therapy Oncology Group grading system. Results:Three months after the end of radiotherapy, 59.2% and 40.7% of patients showed grade 0 skin toxicity and grade 1 skin toxicity, respectively. After 6 months, 70.4% and 29.6% of patients showed grade 0 and grade 1 skin toxicity. After 1 year, grade 0 skin toxicity was found in 77.7% of the patients and grade 1 skin toxicity in 22.2% of the patients. After 18 months, grade 0 skin toxicity was found in 92.6% and grade 1 skin toxicity in 7.4% of the patients. After a median follow-up of 24 months, all patients showed excellent cosmetic results with minimal breast edema and minimal skin changes. There have been no local relapses to date. Conclusion:The accelerated hypofractionated schedule with a concomitant boost appears to be an acceptable alternative to the traditional longer schedule, with low local toxicity and excellent to good short-term cosmetic results, although a much longer follow-up is needed to assess the local control rate.

Long-term survival of a patient with multiple abdominal metastasis from endometrial carcinoma treated with multi-portal conformal re-irradiation and chemotherapy.

A patient with recurrent endometrial cancer with multiple abdominal and pelvic tumoral masses was treated with re-irradiation combined with liposomal doxorubicin and oxaliplatin. A multiple field conformal technique was used to deliver a highly accelerated and hypofractionated scheme (15 fractions of 3.5 Gy, within 19 days). Complete response was confirmed four months after therapy. Four years later a lung metastasis appeared and was again treated with a similar course of therapy, once again resulting in a complete response. It is suggested that in the era of modern image-guided radiotherapy patients with endometrial cancer who have relapsed within or outside the loco-regional area, should be carefully assessed for an eventual gross tumor eradication using high-dose localized radiotherapy, leaving as the only target of chemotherapy the microscopic undetectable disease.

Concurrent administration of liposomal doxorubicin improves the survival of patients with invasive bladder cancer undergoing hypofractionated accelerated radiotherapy (HypoARC)

Cisplatin-based radio-chemotherapy is an effective alternative to cystectomy. The position of cisplatin has been challenged by novel drugs, while altered radiotherapy fractionation is also tested against conventional radiotherapy (RT). This study focuses on liposomal doxorubicin (LDox) in combination with an aggressive radiotherapy scheme (HypoARC). Eighty-two bladder cancer patients were treated with hypofractionated/accelerated RT (14xa0×xa02.7xa0Gy to the pelvis and 15xa0×xa03.4xa0Gy to the bladder, within 19xa0days), supported with amifostine (0–1,000xa0mg sc.). Forty-one out of 82 patients received concurrently LDox (20xa0mg/m2 for 3 bi-weekly cycles). LDox was free of haematological toxicity, erythordysestesia grade 1 being the only side effect noted in 5/41 patients. Although the incidence of early toxicities did not increase with LDox, delays of radiotherapy were increased (Pxa0=xa00.16). Amifostine significantly protected patients against toxicities and delays. There were no severe late complications recorded. Complete response rate was similar in both groups (85.4 vs. 87.8%). The 3-year local relapse-free survival was better in patients receiving LDox, but at a non-statistical level (64 vs. 47%; Pxa0=xa00.59). The 3-year survival rate was significantly improved in T2-4 stage patients receiving LDox (72.1 vs. 58.7%; Pxa0=xa00.04). Multivariate analysis did not identify any independent prognostic variables of relapse or death events. LDox is a well-tolerated drug during pelvic radiotherapy. Although its efficacy in terms of bladder tumour control rates could not be substantiated due to the high efficacy of the HypoARC regimen applied, survival was improved suggesting either a spatial co-operation or a radio-sensitization of pelvic in-field subclinical disease.

Intraoperative radiation therapy (IORT) in head and neck cancer: A systematic review.

Background:Multimodality therapy constitutes the standard treatment of advanced and recurrent head and neck cancer. Since locoregional recurrence comprises a major obstacle in attaining cure, the role of intraoperative radiation therapy (IORT) as an add-on in improving survival and local control of the disease has been investigated. IORT allows delivery of a single tumoricidal dose of radiation to areas of potential residual microscopic disease while minimizing doses to normal tissues. Advantages of IORT include the conformal delivery of a large dose of radiation in an exposed and precisely defined tumor bed, minimizing the risk of a geographic miss creating the potential for subsequent dose reduction of external beam radiation therapy (EBRT). This strategy allows for shortening overall treatment time and dose escalation. The aim of this review is to summarize recent published work on the use of IORT as an adjuvant modality to treat common head and neck cancer in the primary or recurrent setting. Methods:We searched the Medline, Scopus, Ovid, Cochrane, Embase, and ISI Web of Science databases for articles published from 1980 up to March 2016. Results:Based on relevant publications it appears that including IORT in the multimodal treatment may contribute to improved local control. However, the benefit in overall survival is not so clear. Conclusion:IORT seems to be a safe, promising adjunct in the management of head and neck cancer and yet further well organized clinical trials are required to determine its role more precisely.

A Retrospective Analysis of Toxicity and Efficacy for 2 Hypofractionated Irradiation Schedules Versus a Conventional One for Post-Mastectomy Adjuvant Radiotherapy in Breast Cancer

Introduction: The aim of this analysis was a retrospective evaluation of the efficacy and toxicity of 2 hypofractionated irradiation schedules compared to conventional therapy in post-mastectomy patients. Methods: 3 irradiation schedules were analyzed: 48.30 Gy in 21 fractions (group A, n = 60), 42.56 Gy in 16 fractions (group B, n = 27) and 50 Gy in 25 fractions (group C, n = 30) of the front chest wall. All groups were also treated with a supraclavicular field, with 39.10 Gy in 17 fractions (group A), 37.24 Gy in 14 fractions (group B) or 45 Gy in 25 fractions (group C). Results: No local recurrences were noted in any group during 36 months of follow-up. Acute skin toxicity presented in all groups, with 58.3%, 70.4% and 60% of grade I; 35%, 25.9% and 40% of grade II; 6.7%, 3.7% and 0% of grade III being seen in groups A, B and C, respectively. Late skin toxicity was noted only as grade I in 16.7%, 25.9% and 26.7% of groups A, B and C, respectively. No significant difference was noted among all groups for either acute or late skin toxicity, or for radio-pneumonitis (chi2 test, p > 0.05). Conclusion: All schedules were equally effective with equivalent toxicity. A prospective randomized study is needed to confirm our results.

Radiotherapy of early breast cancer in scleroderma patients: our experience with four cases and a short review of the literature

PURPOSEnConnective vascular diseases (CVD), including scleroderma, are reported to represent for some researchers a relative contraindication and for others absolute contraindication for radiotherapy. The purpose of our study is to add four new cases to the existing body of international literature and to determine whether women with pre-existing scleroderma who have been surgically treated for early breast cancer could undergo postsurgical radiotherapy without serious early and late complications.nnnPATIENTS AND METHODSnFrom May 1998 to November 2010, we irradiated for early breast cancer four patients suffering from pre-existing scleroderma; after conservative surgery, we performed whole breast postoperative radiotherapy of 50.4 Gy total dose to the whole breast plus a 9 Gy boost to the tumor bed. We reviewed the records of all four patients and evaluated the early and late reactions using acute radiation morbidity scoring criteria (Radiation Therapy Oncology Group [RTOG], American College of Radiology, Philadelphia, PA) and late radiation morbidity scoring scheme (European Organisation for Research and Treatment of Cancer [EORTC], Brussels, Belgium and RTOG).nnnRESULTSnAfter a median follow-up of 105 months (range 12-155 months) the early and late toxicity concerning the skin, the subcutaneous tissues, the lungs, and the heart have been acceptable and are in full accordance with what have been reported in international literature.nnnCONCLUSIONnThis study matches global experience, which shows that patients with scleroderma and breast cancer must be discussed by the multidisciplinary tumor board in order for a personalized treatment strategy to be formulated. Radiation therapy can be proposed as a postsurgical therapeutic option in selected cases.