F. Cavagnetto

Adjuvant intraoperative radiotherapy for selected breast cancers in previously irradiated women: Evidence for excellent feasibility and favorable outcomes

BACKGROUND The present report provides preliminary outcomes with intraoperative radiotherapy delivered to women with breast cancer included in a re-irradiation program. MATERIALS AND METHODS From October 2010 to April 2014, thirty women were included in a re-irradiation protocol by exploiting IORT technique. The median time between the two irradiations was 10 years (range 3-50). All patients underwent conservative surgery, sentinel lymph node excision and IORT with electron beam delivered by a mobile linear accelerator. Primary endpoint was esthetic result and consequential/late toxicity; secondary endpoints were local control (LC), disease free survival (DFS) and overall survival (OS). RESULTS With a median follow up of 47 months (range 10-78), we analyzed 29 patients (1 lost at follow up). Twenty-seven patients (90%) had presented breast cancer local relapse or a new primary cancer in the same breast after a previous conservative surgery plus radiation treatment; three patients (10%) had previously received irradiation with mantle field for Hodgkin Lymphoma. Esthetic result was excellent in 3 pts (10%), good in 12 pts (41%), fair in 8 pts (28%) and poor in 6 pts (21%). 12 (41%) patients showed subcutaneous fibrosis at the last follow-up. LC, DFS and OS at five years was 92.3%, 86.3% and 91.2%, respectively. CONCLUSION Although we analyzed a small number of patients, our results are satisfactory and this approach is feasible even if it could not be considered the standard treatment. Further clinical trials exploring IORT are needed to identify possible subgroups of patients that might be suitable for this type of approach.

Radio-hyperthermia in post-surgical recurrence of melanoma

Aims and background Malignant melanoma is one of the most radioresistant tumors. It can be treated with combinated hyperthermia and radiation therapy. Methods From January 1991 through June 1992, 7 patients, 1 male and 6 female, aged 40-88 years (mean 75), with skin and nodal postsurgical recurrences of melanoma, were treated with a combination of radiation therapy and hyperthermia. Two patients presented systemic disease when they reached our observation, but all of them were without symptoms. None of them underwent surgical excision of the recurrence before or during thermoradiotherapy. None received chemotherapy for these recurrences or had received radiotherapy in the past. They were irradiated with electron beams, with electron energies selected according to the depth of the lesions. The total dose was 40 Gy in 10 fractions in 5 weeks. Hyperthermia was administered for 10 minutes to 1 hour after irradiation. An inductive method of radiofrequency heating at 434 of 915 MHz was used depending on the depth of the lesions. In all of these treatments a ionized water bolus was used. The prescribed hyperthermic dose was 42 °C for half a hour. The treatments were carried out twice a week for 5 weeks. A fiberoptic multichannel thermometer was used for thermometry. Results Four patients (57 %) achieved a complete response, 2 patients (29 %) a partial response, and 1 patient (14 %) stabilization. We found no correlation between tumor volume and response rate. Site effects and complications of the treatment were minimal (moderate erythema). Conclusions Our results are in the wide range of values reported in the literature.

Image Guided Hypofractionated Radiotherapy by Helical Tomotherapy for Prostate Carcinoma: Toxicity and Impact on Nadir PSA

Aim. To evaluate the toxicity of a hypofractionated schedule for primary radiotherapy (RT) of prostate cancer as well as the value of the nadir PSA (nPSA) and time to nadir PSA (tnPSA) as surrogate efficacy of treatment. Material and Methods. Eighty patients underwent hypofractionated schedule by Helical Tomotherapy (HT). A dose of 70.2 Gy was administered in 27 daily fractions of 2.6 Gy. Acute and late toxicities were graded on the RTOG/EORTC scales. The nPSA and the tnPSA for patients treated with exclusive RT were compared to an equal cohort of 20 patients treated with conventional fractionation and standard conformal radiotherapy. Results. Most of patients (83%) did not develop acute gastrointestinal (GI) toxicity and 50% did not present genitourinary (GU) toxicity. After a median follow-up of 36 months only grade 1 of GU and GI was reported in 6 and 3 patients as late toxicity. Average tnPSA was 30 months. The median value of nPSA after exclusive RT with HT was 0.28 ng/mL and was significantly lower than the median nPSA (0.67 ng/mL) of the conventionally treated cohort (P = 0.02). Conclusions. Hypofractionated RT schedule with HT for prostate cancer treatment reports very low toxicity and reaches a low level of nPSA that might correlate with good outcomes.

Dosimetric analysis of Tomotherapy-based intracranial stereotactic radiosurgery of brain metastasis

PURPOSE This paper analyzes Tomotherapy-based intracranial stereotactic radiosurgery (HTSRS) of brain metastasis targeting two end-points: 1) evaluation of dose homogeneity, conformity and gradient scores for single and multiple lesions and 2) assay of dosimetric criticality of completion of HTSRS procedures. METHODS 42 treatment plans of 33 patients (53 brain lesions) treated with HTSRS were analyzed. Dose to healthy brain, homogeneity, conformity and gradient indexes were evaluated for each lesion. Influence of Field Length and multiple lesions cross-talk effect were assessed. Treatment interruption and completion was investigated using radiochromic films in order to examine the delivered dose and its robustness to patient intrafraction movement. RESULTS The average dose homogeneity index was 1.04 ± 0.02 (SD). Average dose conformity and gradient score indexes were 1.4 ± 0.2 and 50 ± 14 respectively. We found a strong correlation of the dose to healthy brain and conformity and gradient indexes with target(s) volume for which analytical functions were obtained. Field Length and cross-talk effect were significantly correlated with poor gradient scores, but were found not to affect dose conformity. CONCLUSIONS Homogeneity and conformity of HTSRS plans achieved excellent scores, while dose falloff and dose to healthy brain were slightly larger when compared with non-coplanar SRS techniques. Care should be given if treating large (>3 cc) or multiple near in-plane lesions in order to reduce dose to healthy brain. Analysis of interrupted treatments suggests splitting HTSRS treatments in two consecutive fractions in order to prevent target miss and overdosage due to patient intrafraction movement.

Moderate hypofractionated radiotherapy after prostatectomy for cancer patients: toxicity and clinical outcome

Background After radical prostatectomy (RP) radiotherapy (RT) plays a role, both as adjuvant or salvage treatment. If negative features are present such as extracapsular extension, seminal vesicle invasion, lymph invasion, and positive surgical margins, RT after RP reduces the risk of recurrence, although it is associated with an increased risk of acute and late toxicities. An intensified RT delivered in a shortened time could improve clinical outcome and be safely combined with hormonal therapy (HT). The aim of this study was to determine the acute and late toxicities associated with hypofractionated RT and to assess the impact of the addition of HT to RT in high-risk prostate cancer (PC) patients on overall response and toxicity. Materials and methods Sixty-four PC patients undergoing RP were included in this retrospective study. All patients were recommended to receive adjuvant or salvage RT. Prescription doses were 62.5 Gy in 25 fractions to prostate bed, 56.25 Gy in 25 fractions to seminal vesicles bed, and 50 Gy in 25 fractions to pelvis if indicated. HT was administered to patients with additional adverse pathologic features including Gleason score >7, prostate-specific antigen >20 ng/mL before surgery, or prostate-specific antigen with rapid doubling time after relapse or nodal involvement. After completion of RT, patients were observed after 4 weeks, and then followed-up every 3–6 months. Acute and late toxicities were assessed using Common Terminology Criteria for Adverse Events v4 and Radiation Therapy Oncology Group scale, respectively. Results For acute toxicity, only grade 1 gastrointestinal and genitourinary toxicities were detected in 17% and 11% of patients, respectively. As regards late toxicity, only 5% of the patients developed grade 1 gastrointestinal adverse event; grade 1, grade 2, and grade 3 genitourinary toxicity was recorded in 5%, 3.3%, and 3.3% of patients, respectively. Two and 5 years overall survival were 98% and 96%, respectively. The curves stratified for treatment show a slight difference between patients receiving RT or RT+HT, but the differences did not reach statistical significance (p=0.133). Conclusion In patients with PC undergoing RP, hypofractionated RT may contribute to achieve a high overall survival with an acceptable toxicity profile. Combination of RT and HT is also well tolerated and efficacious.

Tumor Size-driven Dose of Intraoperative Radiotherapy for Breast Cancer: 18 Gy Versus 21 Gy

Aim: To test whether a reduced total single dose of 18 Gy of intraoperative radiotherapy with electrons (IORT) may be tailored to safely treat patients in comparison with the standard dose of 21 Gy. (NCT01276938). Patients and Methods: From October 2009 to December 2011, 199 females affected by breast cancer were treated with conservative surgery and IORT with two different exclusive doses, 18 or 21 Gy. Results: The median follow-up was 91 months (16-104 months). Sixty-five patients (pT1a\b, pN0\mic, pMx, G1-G3) received 18 Gy and 134 patients (pT1c\2, pN0\mic, pMx, G1-G3) received 21 Gy. No significant difference in local recurrence-free survival or overall survival was detected in the 18 Gy-treated arm versus that treated with 21 Gy: 96.9% vs. 96.3%, p=0.72, and 96.9% vs. 95.5%, p=0.82, respectively at 5 years. Conclusion: The lower dose of 18 Gy achieved excellent results in terms of local toxicity and local control in early breast cancer.

Neuroendocrine late effects after tailored photon radiotherapy for children with low grade gliomas: Long term correlation with tumour and treatment parameters

PURPOSE To evaluate neuroendocrine late effects in paediatric patients with low grade glioma (LGG) who underwent radiotherapy. METHODS AND MATERIAL We performed a retrospective evaluation of 40 children with LGG treated from July 2002 to January 2015 with external radiotherapy. Tumour locations were cerebral hemisphere (n=2); posterior fossa (n=15); hypothalamic-pituitary axis (HPA, n=15); spine (n=5). Three patients presented a diffuse disease. We looked for a correlation between endocrine toxicity and tumour and treatment parameters. The impact of some clinical and demographic factors on endocrinal and neuro toxicity was evaluated using the log-rank test. RESULTS The median follow-up was 52months (range: 2-151). Median age at irradiation was 6. The dose to the HPA was significantly associated with endocrine toxicity (P value=0.0190). Patients who received chemotherapy before radiotherapy and younger patients, showed worse performance status and lower IQ. The 5-year overall survival (OS) and progression free survival (PFS) rates were 94% and 73.7%, respectively. CONCLUSION Radiotherapy showed excellent OS and PFS rates and acceptable late neuroendocrine toxicity profile in this population of LGG patients treated over a period of 13years. In our experience, the dose to the HPA was predictive of the risk of late endocrine toxicity.

PO-0993: Intra-operative radiotherapy for prostate cancer: preliminary midterm results of a mono institutional study

was then possible to develop software for calculating the dose distribution at any angle made of the applicator with the surface. Results: The software calculates the dose distribution by varying the angle and the depth to which you want to know. The variation of homogeneity is very important. For an angle of 25°, the inhomogeneity in the surface plane is between 100 and 40 %. Conclusions: A software has been developed, based on the computation code PENELOPE to know the dose distribution at any depth as a function of angle applicator with the surface.