Intraoperative Examination of Retro-Areolar Margin is not Routinely Necessary During Nipple-Sparing Mastectomy for Cancer.

BACKGROUND: Intraoperative examination of retro-areolar margin (IERM) often is used during nipple-sparing mastectomy (NSM) for cancer, but there is no robust data regarding its real advantage. METHODS: Consecutive patients undergoing NSM for cancer with omission of IERM according to institutional protocols from 2016 to 2021 were retrospectively analyzed. The decision to maintain or remove the Nipple-Areola Complex (NAC) after definitive pathology was taken at the multidisciplinary meeting. RESULTS: Among 162 women operated in the study period, the presence of neoplastic cells within 2 mm from the inked retroareolar margin (RAM) was detected at permanent pathology in 17 cases (10.5%). Nipple-Areola-Complex (NAC) was removed postoperatively in five patients (3%) for margins <1 mm, the other 12 were observed, whereas postoperative NAC necrosis required surgical removal in additional five cases (3%). The NAC was thus preserved in 152 of 162 patients (94%). At multivariate analysis, RAM ≤2 mm was associated with radiological tumor-to-nipple distance less than or equal to 1 cm (p = 0.04) and Ki67 label index ≥ 20 (p = 0.04), whereas multifocality/multicentricity showed a trend towards significance (p = 0.07). At a median follow-up of 46 months, five locoregional relapses occurred (3%), only one of them involving the NAC (0, 6%). Locoregional relapse and overall survival for patients with RAM > or < 2 mm were not different. CONCLUSIONS: IERM is not routinely necessary during NSM for cancer, because its omission is associated with a very low return to the operating room, it is oncologically safe, and associated pitfalls are avoided. Further studies are necessary to confirm these findings.

Long-Term Outcomes of Once-Daily Accelerated Partial-Breast Irradiation With Tomotherapy: Results of a Phase 2 Trial.

PURPOSE: We report long-term outcomes of phase 2 trial on patients with invasive breast cancer treated with accelerated partial-breast irradiation (APBI) using tomotherapy after breast conservative surgery. METHODS AND MATERIALS: From December 2010 to December 2018, we treated 338 women with APBI-tomotherapy: 38.5 Gy in 10 once-daily fractions. Patients selected were age ≥50 years old, with ≤3 cm in size unifocal tumor and at least 2 mm of clear margins. Disease outcomes were analyzed by clinicopathologic characteristics, molecular phenotypes, and American Society for Radiation Oncology (ASTRO) 2017 updated consensus groupings. RESULTS: The median age was 65 years (range, 50-86). The invasive ductal (87.5%) and the luminal A-like molecular phenotype (70%) were the most common tumors. Overall 242 patients (71.6%) were considered "suitable" for enrollment in APBI according to the eligibility criteria of the ASTRO-2017 consensus statement. With a median follow-up of 76 months (range, 17-113), 2 patients (0.6%) had an invasive ipsilateral breast tumor recurrence (IBTR), and 2 patients (0.6%) had an axillary ipsilateral failure. The rate of local control in terms of free of IBTR was 99.4% and locoregional control (no recurrence in ipsilateral breast as well as in regional nodes) was 98.8%. Progression-free survival was 98.4% and 92% at 5 and 10 years, respectively. Acute and late skin toxicity, graded according to the Common Terminology Criteria for Adverse Events, were 7.7% (G1) and 0.6% (G2) and 4.4% (G1) and 1.1% (G2), respectively. There were no grade 3/4 toxicities, however. Very few patients (2%) or physicians (2%) assessed cosmetic outcome as fair or poor at the 2-year follow-up. CONCLUSIONS: This phase 2 trial on APBI-tomotherapy shows excellent long-term results. Once-daily fractionation schedule was well tolerated with a low rate of adverse events and worse cosmetic outcome. In this series, even among those deemed cautionary or unsuitable for APBI by ASTRO criteria, we demonstrated a low rate of IBTR.

Three-dimensional surface and ultrasound imaging for daily IGRT of prostate cancer.

BACKGROUND: Image guided radiotherapy (IGRT) is an essential pre-requisite for delivering high precision radiotherapy. We compared daily variation detected by two non-ionizing imaging modalities (surface imaging and trans-abdominal ultrasound, US) to verify prostate patient setup and internal organ variations. METHODS: Forty patients with organ confined prostate cancer and candidates to curative radiotherapy were enrolled in this prospective study. At each treatment session, after laser alignment, all patients received imaging by a 3D-surface and a 3D-US system. The shifts along the three directions (anterior-posterior AP, cranial-caudal CC, and later-lateral LL) were measured in terms of systematic and random errors. Then, we performed statistical analysis on the differences and the possible correlations between the two modalities. RESULTS: For both IGRT modalities, surface imaging and US, 1318 acquisitions were collected. According with Shapiro Wilk test, the positioning error distributions were not Gaussian for both modalities. The differences between the systematic errors detected by the two modalities were statistically significant only in LL direction (p < 0.05), while the differences between the random errors were not statistically significant in any directions. The 95% confidence interval of the residual errors obtained by subtracting the random errors detected with surface images to those detected with US was included in the range from -7 mm to 7 mm corresponding to the minimum PTV margin adopted in AP direction in our clinical routine. CONCLUSIONS: From our data, it emerges that setup misalignments measured by surface imaging can be predictive of US displacements after the adjustment for systematic errors. Moreover, surface imaging can detect setup errors predictive of registration errors measured by US. This data suggest that the two IGRT modalities could be considered as complementary to each other and could represent a daily "low-cost" and non-invasive IGRT modality in prostate cancer patients.

Combined modality therapy for thoracic and head and neck cancers: a review of updated literature based on a consensus meeting.

PURPOSE: Combined modality therapy is a mainstay option for thoracic malignancies and head and neck cancers. The integration of different strategies is based on the multidisciplinary approach of modern clinical oncology. Radiation oncologists have to be educated, trained, and updated to provide state-of-the-art care to cancer patients and thus educational meetings are crucial. METHODS: The Italian Association of Radiation Oncology Young Members Working Group (AIRO Giovani) organized its 8th national meeting, focused on combination therapy in lung, esophageal, and head and neck cancer (with a specific focus on larynx-preservation strategies for larynx/hypopharynx tumors), involving young professionals working in Italy. The meeting was addressed to young radiation oncologists, presenting state-of-the-art knowledge, based on the latest evidence in this field. We performed a review of the current literature based on the highlights of the Congress. RESULTS: The multimodality approach of head and neck and thoracic malignancies includes surgery, chemotherapy, and radiotherapy, but also has to take into account new information and data coming from basic and translational research and including molecular biology, genetics, and immunology. All these aspects are crucial for the treatment of non-small-cell lung cancer and esophageal, esophagogastric junction, and larynx/hypopharynx malignancies. The integration of different treatments in the clinical decision-making process to combine therapies is crucial. CONCLUSIONS: Combination therapy has proved to be a consolidated approach in these specific oncologic settings, highlighting the importance of multimodality management in modern clinical oncology. Dedicated meetings on specific topics are helpful to improve knowledge and skills of young professionals in radiation oncology.

Three-dimensional surface imaging for detection of intra-fraction setup variations during radiotherapy of pelvic tumors.

PURPOSE: Surface-based image guided radiotherapy (IGRT) allows positioning and/or monitoring patients in 3 dimensions (3D), without the use of ionizing radiation. In this study, we report on intra-fraction motion measured by acquisition of multiple images of 3D body surfaces. MATERIALS AND METHODS: Twenty-nine patients treated for pelvic tumors were enrolled. Setup variations (SV) through three consecutive body surfaces acquired by the optical IGRT system Align-RT (Vision-RT, London, UK) were analyzed before, during and at the end of treatment delivery. Displacements along the main axes (X, Y and Z) from initial (I) to mid-treatment (MT) and final (F) acquisitions were recorded. Time and direction of SV were assessed. RESULTS: A total of 6272 images from 792 fractions of 29 patients were available. The main source of misalignment was between I and MT acquisition (p < 0.001). The dominant SV direction was the vertical one (Z axis), with mean SV of -1.20 ± 0.06 mm and -1.55 ± 0.06 mm for I-MT and I-F acquisitions, respectively. The Y mean components of SV were, respectively, -0.95 ± 0.10 mm and -1.0 ± 0.10 for I-MT and I-F acquisitions, while the X deviations were 0.07 ± 0.08 mm for I-MT and 0.26 ± 0.08 mm I-F. CONCLUSION: Three-D surface imaging for patient setup monitoring highlighted remarkable mobility of patients during RT session, especially in the anterior-posterior direction (Z axis). The largest magnitude in patient movements occurred during the first part of delivery. These findings suggest that the initial setup control cannot not to be sufficient to guarantee treatment reproducibility, especially for long-lasting RT treatments.

Radiotherapy for vestibular schwannoma: Review of recent literature results.

BACKGROUND: The management of vestibular schwannoma is still a quite controversial issue and can include wait and see policy, surgery and radiotherapy, mainly with stereotactic technique. The purpose of this study is to review the results of recent clinical series treated by radiotherapy. MATERIALS AND METHODS: Literature search was performed by Pubmed and Scopus by using the words "vestibular schwannoma, acoustic neuroma, radiotherapy, radiosurgery". RESULTS: Management options of VS include wait and see, surgery and radiotherapy. In case of small lesions, literature data report local control rates higher than 90% after radiosurgery (SRS) similar those of surgical techniques. Recent literature reviews show favourable functional outcome by using SRS. Several literature data support the use of fractionated stereotactic radiotherapy (FSRT) in case of large inoperable lesions. CONCLUSION: Radiotherapy plays a relevant role in the treatment of VS. In small-size lesions, SRS can guarantee similar local control and potentially better function outcome compared to surgery. In case of large and irregularly shaped lesions, FSRT can be the used when surgery is not feasible.

Stereotactic radiation therapy for skull base recurrences: Is a salvage approach still possible?

AIM: A literature review was performed to analyse the role of stereotactic radiotherapy given in a single shot or in a fractionated fashion for recurrent skull base tumours in order to ascertain if it can be a real salvage approach. BACKGROUND: The management of recurrent skull base tumours can have a curative or palliative intent and mainly includes surgery and RT. MATERIALS AND METHODS: One-thousand-ninety-one articles were found in the search databases and the most relevant of them were analysed and briefly described. RESULTS: Data on recurrences of meningioma, pituitary adenoma, craniopharyngioma, chordoma and chondrosarcoma, vestibular schwannoma, glomus jugulare tumours, olfactory neuroblastoma and recurrences from head and neck tumours invading the base of skull are reported highlighting the most relevant results in terms of local control, survival, side effects and complications. CONCLUSIONS: In conclusion, it emerges that SRS and FSRT are effective and safe radiation modalities of realize real salvage treatment for recurrent skull base tumours.

Postoperative radiotherapy in prostate cancer: Analysis of prognostic factors in a series of 282 patients.

AIM: To assess the outcomes of patients treated with postoperative RT in relation to the possible prognostic factors. BACKGROUND: Postoperative radiotherapy (RT) has been proved to reduce the risk of biochemical recurrence in high-risk prostate cancer patients. Baseline prostate specific antigen (PSA), pathological Gleason score (GS), positive surgical margins, nodal status and seminal vesicle invasion are independent predictors of biochemical relapse. MATERIALS AND METHODS: The clinical records of 282 patients who underwent postoperative RT were retrospectively reviewed. The prognostic value of postoperative PSA, preoperative risk class, nodal status, pathological GS, margins status, and administration of hormonal therapy (HT) was analyzed. RESULTS: Postoperative RT was delivered with a median dose to the prostatic fossa of 66 Gy (range 50-72) in 1.8-2 Gy/fraction. Median follow-up was 23.1 months (range 6-119). Five-year actuarial biochemical disease-free survival (bDFS) and overall survival rates were 76% and 95%, respectively. Higher bDFS was found for patients with postoperative PSA <0.02 ng/ml (p = 0.03), low preoperative risk class (p = 0.01), pN0 (p = 0.003), GS 4-6 (p = 0.0006), no androgen deprivation therapy (p = 0.02), and irrespective of surgical margin status (p = 0.10). Multivariate analysis showed that postoperative PSA and Gleason score had a significant impact on bDFS (p = 0.039 and p = 0.05, respectively). CONCLUSIONS: Postoperative RT with a dose of 66 Gy offers an acceptable toxicity and an optimal disease control after radical prostatectomy in patients with different risk features. A postoperative PSA >0.02 ng/ml could be considered as a prognostic factor and a tool to select patients at risk for progression.

Prone versus supine position for adjuvant breast radiotherapy: a prospective study in patients with pendulous breasts.

PURPOSE: To analyze dosimetric parameters of patients receiving adjuvant breast radiotherapy (RT) in the prone versus supine position. METHODS AND MATERIALS: Forty-one out of 55 patients with pendulous breasts and candidates for adjuvant RT were enrolled in the study after informed consent. They underwent computed tomography (CT)-simulation in both prone and supine position. Target and non target volumes were outlined on CT images. Prescribed dose was 50 Gy delivered by two tangential photon fields followed by 10 Gy electron boost. Target coverage and dose homogeneity to clinical target volume (CTV) and planning target volume (PTV) were assessed by V95, V105 and V107 and dose to lung, heart and left anterior descending coronary artery (LAD) by V5, V10, V20, and mean and maximum dose. Data were analyzed by Student's t-test. RESULTS: CTV and PTV coverage was significantly better in supine than in prone position. Lung V5, V10, and V20 were significantly lower in prone than in supine position. Heart V5, V10, V20, and LAD mean and maximum dose, in the 17 patients with left breast tumor, were lower in prone than in supine position, but without statistical significance. Based on treatment planning data and on treatment feasibility, 29/41 patients (70.7%) were treated in prone position. Acute and late toxicities of patients treated in prone and in supine position were not statistically different. CONCLUSION: Prone position is a favorable alternative for irradiation of mammary gland in patients with pendulous breasts and in our series was adopted in 71% of the cases.

Radical prostatectomy and intraoperative radiation therapy in high-risk prostate cancer.

Intraoperative electron beam radiotherapy (IOERT) for prostate cancer (PC) is a radiotherapeutic technique, giving high doses of radiation during radical prostatectomy (RP). This paper presents the published treatment approaches for intraoperative radiotherapy analyzing functional outcome, morbidity, and oncological outcome in patients with clinical intermediate-high-risk prostate cancer. A systematic review of the literature was performed, searching PubMed and Web of Science. A "free text" protocol using the term intraoperative radiotherapy and prostate cancer was applied. Ten records were retrieved and analyzed including more than 150 prostate cancer patients treated with IOERT. IOERT represents a feasible technique with acceptable surgical time and minimal toxicity. A greater number of cases and longer follow-up time are needed in order to assess the long-term side effects and oncological outcome.

Single-arm phase II study of conformal radiation therapy and temozolomide plus fractionated stereotactic conformal boost in high-grade gliomas: final report.

PURPOSE: To assess survival, local control and toxicity using fractionated stereotactic conformal radiotherapy (FSCRT) boost and temozolomide in high-grade gliomas (HGGs). PATIENTS AND METHODS: Patients affected by HGG, with a CTV(1)(clinical target volume, representing tumor bed ± residual tumor + a margin of 5 mm) ≤ 8 cm were enrolled into this phase II study. Radiotherapy (RT, total dose 6,940 cGy) was administered using a combination of two different techniques: three-dimensional conformal radiotherapy (3D-CRT, to achieve a dose of 5,040 or 5,940 cGy) and FSCRT boost (19 or 10 Gy) tailored by CTV(1)diameter (≤ 6 cm and > 6 cm, respectively). Temozolomide (75 mg/m(2)) was administered during the first 2 or 4 weeks of RT. After the end of RT, temozolomide (150-200 mg/m(2)) was administered for at least six cycles. The sample size of 41 patients was assessed by the single proportion-powered analysis. RESULTS: 41 patients (36 with glioblastoma multiforme [GBM] and five with anaplastic astrocytoma [AA]) were enrolled; RTOG neurological toxicities G1-2 and G3 were 12% and 3%, respectively. Two cases of radionecrosis were observed. At a median follow-up of 44 months (range 6-56 months), global and GBM median overall survival (OS) were 30 and 28 months. The 2-year survival rate was significantly better compared to the standard treatment (63% vs. 26.5%; p < 0.00001). Median progression-free survival (PFS) was 11 months, in GBM patients 10 months. CONCLUSION: FSCRT boost plus temozolomide is well tolerated and seems to increase survival compared to the standard treatment in patients with HGG.

Radiotherapy and concomitant temozolomide during the first and last weeks in high grade gliomas: long-term analysis of a phase II study.

We tested the efficacy and safety of temozolomide (TMZ) when given concomitantly to radiotherapy only in the first and last weeks of treatment to patients affected by high grade gliomas. Conformal radiotherapy (CTV1: tumor bed + residual tumor if present + 1.5 cm, 5,940 cGy, 180 cGy/day; CTV2: oedema, 3,960 cGy, 180 cGy/day) was associated with TMZ, 75 mg/m(2) x 5 days, the first and last weeks of radiotherapy. Adjuvant chemotherapy with TMZ (150 mg/mq daily x 5 days, q28 on the first cycle, 200 mg/mq daily x 5 days, q28 for the following cycles) was given, after chemoradiation, until disease progression or up to 6 cycles. From October 2000 to December 2003, 29 patients (25 GBL, 86.2%; 4 AA, 13.8%) were enrolled in this study. Twenty-two patients (75.8%) received a median 6 cycles of adjuvant chemotherapy with TMZ (range 1-20). Hematological toxicity was absent during concomitant chemoradiation and mild in adjuvant therapy, while neurological toxicity (seizures) was observed only in one case. At a median follow-up of 66 months (range 3-96), median progression-free survival (PFS) was 8 months, with a 1- and 2-year PFS of 46.7 and 28.7%, respectively; median overall survival (OS) time was 21 months, with a 1- and 2-year OS of 69.2 and 42.3%, respectively. In our experience, TMZ proved to be effective even when given only during the first and the last week of radiotherapy, with lower hematological toxicity.

Compensation for gaps in radiotherapy: suggested teaching approach to its calculation.

Unplanned gaps in radiotherapy can impact on its clinical effect, especially in tumors with accelerated repopulation. In the literature, several technical solutions have been proposed. According to the situation, compensation for the effect on the tumor to the detriment of normal tissue tolerance can be achieved. An approach, modulated according to the gap duration and timing is proposed aimed at constant tumor control with no significant increased risk of side-effects. The decisional algorithm and calculation formulae are used in our center in teaching addressed to residents to make them familiar with the possible clinical applications of radiobiological knowledge.