Simultaneous Integrated Boost in Once-weekly Hypofractionated Radiotherapy for Breast Cancer in the Elderly: Preliminary Evidence.

AIM: To evaluate once-weekly hypofractionated radiotherapy in elderly patients affected by early breast cancer, reporting acute and late toxicity profiles, and treatment feasibility. PATIENTS AND METHODS: Fifty patients were treated with a hypofractionated regimen: 28.5±2.5 Gy in five fractions at one fraction weekly. Simultaneous integrated boost (SIB) to the tumor bed in high-risk cases. INCLUSION CRITERIA: patients over 70 years old, pT1-2, N0-1a. Acute and late toxicities were assessed based on Radiation Therapy Oncology Group. RESULTS: The median follow-up was 20 months and the median patient age was 79 years. SIB was added for 22 patients (44%). Grade 3-4 acute cutaneous toxicities were not observed; grade 2 toxicity occurred only in four patients (8%). Late subcutaneous tissue toxicity consisted of grade 2 fibrosis in two patients (4%), grade 1 in five (10%) and grade 0 in 41(85%). CONCLUSION: Limiting fraction numbers with a safer profile may improve the management of breast cancer for the elderly.

Comparison of Local Recurrence Among Early Breast Cancer Patients Treated With Electron Intraoperative Radiotherapy vs Hypofractionated Photon Radiotherapy an Observational Study.

PURPOSE: To evaluate local recurrence (LR) in women with early breast cancer (BC) who underwent intraoperative radiation therapy with electrons particles (IORT-E) or adjuvant hypofractionated external radiotherapy (HYPOFX). MATERIALS AND METHODS: We retrospectively analyzed 470 patients with early BC treated at our center from September 2009 to December 2012. 235 women were treated with breast-conserving surgery and immediate IORT-E (21 Gy/1 fraction) while 235 patients underwent wide excision followed by hypofractionated whole-breast irradiation. Radiotherapy modality was chosen according to an individualized decision based on tumor features, stage, technical feasibility, age, and acceptance to be enrolled in the IORT-E group. RESULTS: After a median follow-up of 6 years, we observed 8 (3.4%) and 1 (0.42%) LR in the IORT-E and in the HYPOFX group (p = 0.02), respectively. The two groups differed in the prevalence of clinical characteristics (p < 0.05): age, tumor size, surgical margins, receptors, ki67, and histology. 4 and 1 woman in the IORT-E and HYPOFX group died of BC, respectively (p = 0.167). OS and DFS hazard ratio [HR] were 2.14 (95% IC, 1.10-4.15) and 2.09 (95% IC, 1.17-3.73), respectively. CONCLUSION: Our comparison showed that IORT-E and HYPOFX are two effective radiotherapy modalities after conservative surgery in early BC. However, at 6 years a significant higher rate of LR occurred in patients submitted to IORT-E with respect to HYPOFX. This finding may be correlated to some subsets of patients who, depending on the biological characteristics of the BC, may be less suitable to IORT-E.

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.

Complete response in a patient with gynecological hidradenocarcinoma treated with exclusive external beam radiotherapy and brachytherapy: a case report.

Hidradenocarcinoma (HC) is a very rare disease. This case report illustrates a successful treatment of a 60-year-old woman with vulvo-vaginal localization of hidradenocarcinoma treated with external beam radiotherapy delivered by helical tomotherapy with a simultaneous integrated boost (SIB), followed by brachytherapy. External beam radiotherapy dose prescription was 50.4 Gy in 28 fractions, five fractions per week to whole pelvis (planning target volume 1 - PTV1), 60.2 Gy in 28 fractions to SIB1 (fundus of uterus and right inguinal node), and 58.8 Gy in 28 fractions to SIB2 (lower/middle third of vagina, paraurethral region and right inguinal lymph nodes). Brachytherapy dose prescription was 28 Gy in 4 fractions for cervix, fundus of uterus and upper third of vagina (HR-CTV1), and 22 Gy in 4 fractions to middle third of vagina and paraurethral region (HR-CTV2). D90 for whole treatment was 91.9 Gy and 86.0 Gy for HR-CTV1 and HR-CTV2, respectively. Patient remained 12-months disease-free without treatment related side effects.

Intensified intensity-modulated radiotherapy in anal cancer with prevalent HPV p16 positivity.

AIM: To investigate the toxicity and response of intensity-modulated radiotherapy schedule intensified with a simultaneous integrated boost in anal canal cancer. METHODS: From March 2009 to March 2014, we retrospectively analyzed 41 consecutive patients treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy for anal canal squamous cell carcinoma at our center. Radiotherapy was delivered via simultaneous integrated boost (SIB) technique by helical tomotherapy, and doses were adapted to two clinical target volumes according to the tumor-node-metastasis (TNM) stage: 50.6 Gy and 41.4 Gy in 23 fractions in T1N0, 52.8 Gy and 43.2 Gy in 24 fractions in T2N0, and 55 Gy and 45 Gy in 25 fractions in all patients with N positive and/or ≥ T3, respectively, to planning target volumes 1 and 2. The most common chemotherapy regimen was 5-fluorouracil and mitomycin-based. Human papilloma virus (HPV) p16 expression was performed by immunohistochemistry and evaluated in the majority of patients. Acute and late toxicity was scored according to CTCAe v 3.0 and RTOG scales. RESULTS: The median follow-up was 30 mo (range: 12-71). Median age was 63 years (range 32-84). The stage of disease was: stage I in 2 patients, stage II in 13 patients, stage IIIA in 12 patients, and stage IIIB in 14 patients, respectively. Two patients were known to be HIV positive (4.9%). HPV p16 expression status was positive in 29/34 (85.3%) patients. The 4-year progression-free survival and overall survival in HPV-positive patients were 78% and 92%, respectively. Acute grade 3 skin and gastrointestinal toxicities were reported in 5% and 7.3% of patients, respectively; patients' compliance to the treatment was good due to a low occurrence of severe acute toxicity, although treatment interruptions due to toxicity were required in 7.3% of patients. At 6 mo from end of treatment, 36/40 (90%) patients obtained complete response; during follow-up, 5 (13.8%) patients presented with disease progression (local or systemic). CONCLUSION: In our experience, intensified SIB-IMRT with chemotherapy is very feasible in clinical practice, with excellent results in terms of overall survival and local control.

Novel 10-fraction breast irradiation in prone and supine position: technical, dosimetric and clinical evaluation.

BACKGROUND: The aim of this study was to evaluate retrospectively the planned dose distribution and acute toxicity of adjuvant hypofractionated whole breast radiotherapy (RT) delivered in the prone vs. supine position. METHODS: Twenty-four patients were enrolled; 12 underwent adjuvant RT with a supine setup and 12 with a prone setup. We included patients according to breast volume (≥500 mL), disease stage (≤pT2/pN1), and clinical/biological features. Patients received a regimen of 35 Gy in 10 fractions for 2.5 weeks, and a concomitant boost of 3/4 Gy in 1 fraction/week. Target coverage was assessed by volume, V90, V95, V100, V103 and V105. Heart, LADCA and ipsilateral lung doses were evaluated according to volume, maximum dose, mean dose, V14, V10 and V5. We evaluated acute skin toxicity during RT, at the end of treatment, and after 1 month according to RTOG scales. RESULTS: Radiobiological equivalence was warranted with satisfactory BED values: considering α/ß = 4 for breast cancer, the 10-fraction schedule equaled 74 or 77 Gy depending on the boost dose (3 Gy vs. 4 Gy, respectively). Toxicity was low and similar for supine and prone treatments. Dose sparing was significant in the ipsilateral lung in the prone position (median Dmax: 28.7 Gy vs. 38.4 Gy; median Dmean: 0.8 Gy vs. 6.3 Gy; median V14: 0.6% vs. 13.5%; median V5: 0 vs. 19.3%, p<0.001). CONCLUSIONS: This novel 10-fraction schedule is feasible and well tolerated; the prone position allows better saving of OARs, with a statistically significant value for the ipsilateral lung.

Assessment and clinical validation of margins for adaptive simultaneous integrated boost in neo-adjuvant radiochemotherapy for rectal cancer.

PURPOSE: An adaptive concomitant boost (ACB) for the neo-adjuvant treatment of rectal cancer was clinically implemented. In this study population margins M(90,90) considering rectal deformation were derived for 10 consecutive patients treated at 18 × 2.3Gy with Helical Tomotherapy (HT) and prospectively validated on 20 additional patients treated with HT, delivering ACB in the last 6 fractions. METHODS: Sectorial margins M(90,90) of the whole and second treatment parts were assessed for 90% population through a method combining the 90% coverage probability maps of rectal positions (CPC90%) with 3D local distance measurements between the CPC90% and a reference rectal contour. M(90,90) were compared with the margins M(90,90)(95%/99%), ensuring CPC90% coverage with 95%/99% confidence level. M(90,90) of the treatment second part were chosen as ACB margins which were clinically validated for each patient by means of %volume missing of CPC5/6 excluded by the ACB margins. RESULTS: The whole treatment M(90,90) ranged between 1.9 mm and 9 mm in the lower-posterior and upper-anterior sectors, respectively. Regarding ACB, M(90,90) were 7 mm in the anterior direction and <5 mm elsewhere. M(90,90)(95%/99%) did not significantly differ from M(90,90). The %volume excluded by the ACB margin was<2% for all male and <5% for 9/10 female patients. The dosimetry impact on R_adapt for the patients with the largest residual error was negligible. CONCLUSIONS: Local deformation measurements confirm an anisotropic motion of rectum once set-up error is rigidly corrected. Margins of 7 mm anterior and 5 mm elsewhere are adequate for ACB. Female patients show a slightly larger residual error.

Radiosurgery with Helical Tomotherapy: Outcomes for Patients with One or Multifocal Brain Metastasis.

To evaluate the feasibility and report the preliminary results for stereotactic radiosurgery (SRS) treatments of single or multiple brain metastases delivered with helical tomotherapy (HT) by means of the InterFix™ Radiosurgery kit. Between September 2010 and August 2012, thirty patients underwent SRS for treatment of 46 brain metastases with a median prescription dose of 20 Gy (range 15-21 Gy). Clinical response was assessed with 2-3 month intervals by magnetic resonance imaging (MRI). Dose distribution indexes were computed and compared with published data for SRS performed with dedicated machines. After a median follow-up of 14 months (range 4-31) the estimated overall survival (OS) rate was 70% at 6 months, 60% at 12 months and 44% at 18 months. Local control (LC) was 72% at 6 months, 65% at 12 months and 50% at 18 months. Acute toxicity as headache and epileptic crisis occurred in only two patients. The mean values of conformity, homogeneity and gradient score indexes were 1.36, 1.04 and 50 respectively. HT-SRS for single or multiple brain metastases appears a reliable technique with encouraging clinical outcomes and competitive dosimetrical results.

Mono-institutional Italian experience with a double-lumen balloon-brachytherapy device for early breast cancer: results at a 5-year minimum follow-up.

AIMS AND BACKGROUND: To report the 5-year minimum follow-up in low-risk breast cancer patients treated with a double-lumen balloon-brachytherapy device in one mono-institutional Italian experience. Local control data and cosmetic outcomes were collected and analyzed. METHODS: Between October 2004 and December 2007, we treated 30 early stage breast cancer patients who underwent conservative surgery followed by adjuvant accelerated partial breast irradiation with a double-lumen balloon-brachytherapy system. Eligibility criteria for the protocol were based on the indications of the American Brachytherapy Society and the American Society of Breast Surgeons. The device was placed inside the lumpectomy cavity during surgery by open technique in all the patients. Computed tomography images and standard X-ray were used for treatment planning. The total irradiation dose was 34 Gy in 10 fractions of 3.4 Gy (twice daily) over 5 days to the lumpectomy cavity. RESULTS: Median follow-up was 80.5 months (range, 60-98). No patient developed local recurrence or distant metastasis. At the end of treatment, there was evidence of a symptomatic seroma in 83% of the total patients, with a yearly decreasing trend. However, the incidence of mild and moderate fibrosis progressively increased. Seventy-seven percent of the patients were satisfied with their cosmetic results. CONCLUSIONS: Our findings reinforce the hypothesis that an accelerated double-lumen balloon-breast brachytherapy catheter in selected low-risk patients is safe, and a favorable cosmetic outcome can be achieved.

Ablative or palliative stereotactic body radiotherapy with helical tomotherapy for primary or metastatic lung tumor.

AIM: To evaluate the feasibility and outcomes of stereotactic body radiotherapy (SBRT) by helical tomotherapy (HT) for patients with primary or secondary lung cancer. PATIENTS AND METHODS: Between March 2009 and January 2012, 56 patients were selected as candidates for the study and were divided into two subgroups. The ablative SBRT group included 27 patients with T1-T2 non-small cell lung cancer who received four to five large-dose fractions in two weeks and the palliative SBRT group included 29 patients with lung metastases treated with eight lower-dose fractions in four weeks. RESULTS: No differences in acute toxicities were found between different fractionation schemes with different overall treatment times. Actuarial local control at 24 months was better for the ablative group (69.6%) than for the palliative one (40.4%) (p=0.0019). CONCLUSION: HT-based SBRT was feasible and well-tolerated. Local control was satisfactory for patients treated with ablative SBRT but unsatisfactory for those treated with palliative SBRT. Outcomes also suggest the use of ablative SBRT fractionation for palliative intent.

Focus on the actual clinical target volume irradiated with intraoperative radiotherapy for breast cancer.

AIM: Intraoperative radiotherapy (IORT) has been investigated as an exclusive adjuvant treatment option for early-stage breast cancer (BC). We analysed our experience on the technical aspects of this innovative approach in terms of identification of breast volume actually to be treated during IORT. PATIENTS AND METHODS: A total of 315 patients at low risk of breast cancer recurrence underwent IORT as exclusive treatment after breast-conservative surgery. To evaluate the breast volume actually irradiated with IORT, we considered a sample of eight patients, chosen retrospectively as having enough clips to identify the tumour bed and IORT site in computed-tomography (CT). The clinical target volume (CTV) was assessed for each patient with two different methods: the first, cc-IORT, was considered during surgery according to the chosen collimator diameter and glandular thickness, while the second, cc-CT, was evaluated through computed-tomography performed after surgery. The cc-CT CTV was obtained by contouring the cc-IORT on the CT section on the basis of the clips placed by the surgeon on the resection margins. RESULTS: In our experience, the 5-cm (50%) and the 6-cm (36%) diameter collimators have been the ones, used the most. The diameter of the collimator used did not appear to adversely affect the satisfactory aesthetic result. The comparison between CTVs showed that glandular breast volume contoured with CT (cc-CT) appeared to be three fold larger than the target identified at surgery and included in the area of chosen collimator (cc-IORT). CONCLUSION: The actual volume of breast gland irradiated with the IORT procedure appears to be larger than expected. This may be due to the area being prepared for IORT by placing tissue compactly.

On-line optimization of intraoperative electron beam radiotherapy of the breast.

PURPOSE: To optimize the dose delivery to the breast lumpectomy target treated with intraoperative electron beam radiotherapy (IOERT). MATERIALS AND METHODS: Two tools have been developed in our MU calculation software NEMO X to improve the dose homogeneity and the in-vivo dosimetry effectiveness for IOERT treatments. Given the target (tumor bed) thickness measured by the surgeon, NEMO X can provide auto dose normalization to cover 95% of the target volume with 95% of the prescription dose (PD) and a "best guess" of the expected dosimeter dose (EDD) for a deep seated in-vivo dosimeter. The tools have been validated with the data of 91 patients treated with IOERT on a LIAC mobile accelerator. In-vivo dosimetry has been performed with microMOSFETs positioned on the shielding disk inserted between the tumor bed and the chest wall. RESULTS: On average the auto normalization showed to provide better results if compared to conventional normalization rules in terms of mean target dose (|MTD-PD|/PD ≤ 5% in 95% vs. 53% of pts) and V107 percentage (left angle bracket V107 right angle bracket =19% vs. 32%). In-vivo dosimetry MOSFET dose (MD) showed a better correlation with the EDD guessed by our tool than just by assuming that EDD=PD (|MD-EDD|/EDD ≤ 5% in 57 vs. 26% of pts). CONCLUSIONS: NEMO X provides two useful tools for the on-line optimization of the dose delivery in IOERT. This optimization can help to reduce unnecessary large over-dosage regions and allows introducing reliable action levels for in-vivo dosimetry.

Advances in the implementation of helical tomotherapy-based total marrow irradiation with a novel field junction technique.

Given the limitations in the travel ability of the helical tomotherapy (HT) couch, total marrow irradiation (TMI) has to be split in 2 segments, with the lower limbs treated with feet first orientation. The aim of this work is to present a planning technique useful to reduce the dose inhomogeneity resulting from the matching of the 2 helical dose distributions. Three HT plans were generated for each of the 18 patients enrolled. Upper TMI (UTMI) and lower TMI (LTMI) were planned onto the whole-body computed tomography (CT) and on the lower-limb CT, respectively. A twin lower TMI plan (tLTMI) was designed on the whole-body CT. Agreement between LTMI and tLTMI plans was assessed by computing for each dose-volume histogram (DVH) structure the γ index scored with 1% of dose and volume difference thresholds. UTMI and tLTMI plans were summed together on the whole-body CT, enabling the evaluation of dose inhomogeneity. Moreover, a couple of transition volumes were used to improve the dose uniformity in the abutment region. For every DVH, a number of points >99% passed the γ analysis, validating the method used to generate the twin plan. The planned dose inhomogeneity at the junction level resulted within ±10% of the prescribed dose. Median dose reduction to organs at risk ranged from 30-80% of the prescribed dose. Mean conformity index was 1.41 (range 1.36-1.44) for the whole-body target. The technique provided a "full helical" dose distribution for TMI treatments, which can be considered effective only if the dose agreement between LTMI and tLTMI plans is met. The planning of TMI with HT for the whole body with adequate dose homogeneity and conformity was shown to be feasible.

A biologically competitive 21 days hypofractionation scheme with weekly concomitant boost in breast cancer radiotherapy feasibility acute sub-acute and short term late effects.

BACKGROUND: Radiation therapy after lumpectomy is a standard part of breast conserving therapy for invasive breast carcinoma. The most frequently used schedule worldwide is 60 Gy in 30 fractions in 6 weeks, a time commitment that sporadically may dissuade some otherwise eligible women from undertaking treatment. The purpose and primary endpoint of this perspective study is to evaluate feasibility and short-term late toxicity in a hypofractionated whole breast irradiation schedule. METHODS: Between February and October 2008 we treated 65 consecutive patients with operable invasive early-stage breast cancer with a hypofractionated schedule of external beam radiation therapy. All patients were assigned to 39 Gy in 13 fractions in 3 weeks to the whole breast plus a concomitant weekly boost dose to the lumpectomy cavity of 3 Gy in 3 fractions. RESULTS: All the patients had achieved a median follow up of 24 months (range 21-29 months). At the end of treatment 52% presented grade 0 acute toxicity 39% had grade 1 and 9% had grade 2. At 6 months with all the patients assessed there were 34% case of grade 1 subacute toxicity and 6% of grade 2. At 12 months 43% and 3% of patients presented with clinical grade 1 and grade 2 fibrosis respectively and 5% presented grade 1 hyperpigmentation. The remaining patients were free of side effects. At 24 months, with 56 assessed, just 2 patients (3%) showed grade 2 of late fibrosis. CONCLUSIONS: The clinical results observed showed a reasonably good feasibility of the accelerated hypofractionated schedule in terms of acute, subacute and short-term late toxicity. This useful 13 fractions with a concomitant boost schedule seems, in selected patients, a biologically acceptable alternative to the traditional 30 days regime.

Accelerated partial breast irradiation via the mammosite catheter: preliminary reports of a single-institution experience.

Several studies have shown that the majority of in-breast recurrences following lumpectomy are at or near the original tumor site while ipsilateral breast recurrences further a field occur rarely. This suggests that the radiation dose could be delivered exclusively to the tumor bed, allowing larger fractions to be used without increasing toxicity and shortening the total treatment time. We investigated the use of the MammoSite irradiation system with a view to analyzing complications, cosmesis and patient comfort. Between 2004 and 2007 intracavity brachytherapy was given to 30 patients using the MammoSite device. The reference isodose was prescribed to the lumpectomy cavity with a 1 cm margin. Geometric parameters and anatomic position of the applicator after implantation were checked via CT, x-ray and ultrasound. Analysis was done for patient quality of life, cosmesis, early and late complications. Forty-nine patients received a proposal for MammoSite brachytherapy. Nine declined, 40 enrolled while 10 were excluded for various reasons (Table 5). A total of 30 patients were actually treated to 34 Gy (2 x 3.4 Gy) in 5 days. We observed 3 cases (10%) of infection within 3 months of implantation. Symptomatic seroma was seen in five patients (16.6%) at 6 months, in three (10%) at 12 months, and in just one patient (3.3%) at 18 months. Good to excellent cosmetic results were achieved in 75% by patient and physician ratings. Accelerated partial breast irradiation using the MammoSite catheter produces favorable short-term outcomes, limited toxic effects on skin, and optimal cosmetic results. Patient tolerance for the treatment is very high. Critical issues may regard the importance of good cavity conformance and adequate balloon-skin distance in avoiding possible dose excesses to the skin. For a selected patient group, this could be a valid alternative to conventional whole breast irradiation.