Alberto Testori

Phase I-II study of hypofractionated simultaneous integrated boost using volumetric modulated arc therapy for adjuvant radiation therapy in breast cancer patients: a report of feasibility and early toxicity results in the first 50 treatments

BackgroundTo report results in terms of feasibility and early toxicity of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery.MethodsBetween September 2010 and May 2011, 50 consecutive patients presenting early-stage breast cancer were submitted to adjuvant radiotherapy with SIB-VMAT approach using RapidArc in our Institution (Istituto Clinico Humanitas ICH). Three out of 50 patients were irradiated bilaterally (53 tumours in 50 patients). All patients were enrolled in a phase I-II trial approved by the ICH ethical committee. All 50 patients enrolled in the study underwent VMAT-SIB technique to irradiate the whole breast with concomitant boost irradiation of the tumor bed. Doses to whole breast and surgical bed were 40.5 Gy and 48 Gy respectively, delivered in 15 fractions over 3 weeks. Skin toxicities were recorded during and after treatment according to RTOG acute radiation morbidity scoring criteria with a median follow-up of 12 months (range 8–16). Cosmetic outcomes were assessed as excellent/good or fair/poor.ResultsThe median age of the population was 68 years (range 36–88). According to AJCC staging system, 38 breast lesions were classified as pT1, and 15 as pT2; 49 cases were assessed as N0 and 4 as N1. The maximum acute skin toxicity by the end of treatment was Grade 0 in 20/50 patients, Grade 1 in 32/50, Grade 2 in 0 and Grade 3 in 1/50 (one of the 3 cases of bilateral breast irradiation). No Grade 4 toxicities were observed. All Grade 1 toxicities had resolved within 3 weeks. No significant differences in cosmetic scores on baseline assessment vs. 3 months and 6 months after the treatment were observed: all patients were scored as excellent/good (50/50) compared with baseline; no fair/poor judgment was recorded. No other toxicities or local failures were recorded during follow-up.ConclusionsThe 3-week course of postoperative radiation using VMAT with SIB showed to be feasible and was associated with acceptable acute skin toxicity profile. Long-term follow-up data are needed to assess late toxicity and clinical outcomes.

Surgical Procedures in the DANTE Trial, A Randomized Study of Lung Cancer Early Detection with Spiral Computed Tomography: Comparative Analysis in the Screening and Control Arm

Background: The patient population derived from lung cancer screening programs with low-dose spiral computed tomography (LDCT) is different from the general population accessing thoracic surgical services. Methods: Retrospective review of all surgical cases in the DANTE trial, a randomized study of lung cancer screening with LDCT. Patient characteristics, workup, procedures, resections for benign disease, complications, tumor features, and final outcomes have been analyzed in the LDCT and in the control arm. Results: In the LDCT arm, 77 suspicious lesions were surgically managed in 72 patients. A benign lesion was diagnosed in 17 cases (22%). Major video-assisted thoracoscopic surgery resection was carried out in five lung cancer cases (7%) and segmentectomy in 11 (19%). Complete resection was achieved in 93%, and stage I rate was 73%. Two patients had a local recurrence after open lobectomy, and three had a resectable new primary. In the control group, 28 patients underwent 31 surgical procedures, in five cases (16%) for benign lesions. No major video-assisted thoracoscopic surgery resections were carried out. Resectability rate was 88%, and stage I rate was 52%. Five patients had a local recurrence and two had a second primary. Conclusions: Surgery for benign lesions is a relevant issue in screening-derived patients. Local control may be achieved by minimally invasive techniques or segmentectomy; however, developing the necessary skills requires an effort by the surgical team. Long-term survivors have a noticeable chance of developing second primary cancers or resectable recurrences and may benefit from a second resection.

Clinicopathological and Immunohistochemical Characteristics in Male Breast Cancer: A Retrospective Case Series

BACKGROUND Due to its rarity, male breast cancer (mBC) remains an inadequately characterized disease, and current evidence for treatment derives from female breast cancer (FBC). METHODS We retrospectively analyzed the clinicopathological characteristics, treatment patterns, and outcomes of mBCs treated from 2000 to 2013. RESULTS From a total of 97 patients with mBC, 6 (6.2%) with ductal in situ carcinoma were excluded, and 91 patients with invasive carcinoma were analyzed. Median age was 65 years (range: 25-87 years). Estrogen receptors were positive in 88 patients (96.7%), and progesterone receptors were positive in 84 patients (92.3%). HER-2 was overexpressed in 13 of 85 patients (16%). Median follow-up was 51.5 months (range: 0.5-219.3 months). Five-year progression-free survival (PFS) was 50%, whereas overall survival (OS) was 68.1%. Patients with grades 1 and 2 presented 5-year PFS of 71% versus 22.5% for patients with grade 3 disease; 5-year OS was 85.7% for patients with grades 1 and 2 versus 53.3% of patients with grade 3. Ki-67 score >20% and adjuvant chemotherapy were also statistically significant for OS on univariate analyses. Twenty-six of 87 patients (29.8%) experienced recurrent disease and 16 of 91 patients (17.6%) developed a second neoplasia. CONCLUSION Male breast cancer shows different biological patterns compared with FBC, with higher positive hormone-receptor status and lower HER-2 overexpression. Grade 3 and Ki-67 >20% were associated with shorter OS. IMPLICATIONS FOR PRACTICE There is little evidence that prognostic features established in female breast cancer, such as grading and Ki-67 labeling index, could be applied to male breast cancer as well. This study found that grade 3 was associated with shorter overall survival and a trend for Ki-67 >20%; this could help in choosing the best treatment option in the adjuvant setting. Many questions remain regarding the impact of HER-2 positivity on survival and treatment with adjuvant anti-HER-2 therapy. Regarding metastatic male breast cancer, the results suggest that common regimens of chemo-, endocrine and immunotherapy used in female breast cancer are safe and effective for men. Male breast cancer patients show a higher incidence of second primary tumors, especially prostate and colon cancers and should therefore be carefully monitored.

Protection of right pneumonectomy bronchial sutures with a pedicled thymus flap

A pedicled flap obtained by mobilizing the right lobe of the thymus was used to protect bronchial sutures in 29 consecutive patients undergoing a right pneumonectomy and in 4 additional patients. Fourteen patients had received preoperative chemotherapy with or without radiotherapy. The flap procedure was, in general, easy to do, required an average time of 20.4 minutes, and did not cause added operative morbidity. Postoperative magnetic resonance imaging, performed in 21 of the 29 patients who had pneumonectomy, showed a viable flap in every instance. One bronchopleural fistula occurred in a pneumonectomy patient after induction chemotherapy plus radiotherapy in a patient in the pneumonectomy group in whom adult respiratory distress syndrome developed postoperatively and who required prolonged mechanical ventilation.

Healing of bronchopleural fistula using a modified Dumon stent: A case report

BackgroundBrochopleural fistula following lung resection is a therapeuric challenge for thoracic surgeons.Case presentationWe describe a case of late bronchopleural fistula after right extrapleural pneumonectomy for malignant mesothelioma. Bronchoscopic attempts to repair it were unsuccessful.ConclusionThe use of a modified Y Dumon stent associated with glue apposition on the bronchial stump allowed us to close the fistula without the need of any surgical repair.

Huge malignant phyllodes breast tumor: a real entity in a new era of early breast cancer

Phyllodes tumor is an extremely rare tumor of the breast. It occurs in females in the third and fourth decades. The difficulty in distinguishing between phyllodes tumors and benign fibroadenoma may lead to misdiagnosis. Lymph node involvement is rarely described in phyllodes tumors; for this reason, sentinel node biopsy may be warranted. We present a case of a 33-year-old woman affected by huge tumor of the right breast with ulceration in the skin with a rapid tumor growth and with omolateral axillary metastasis.

Surgical sentinel lymph node biopsy in early breast cancer. Could it be avoided by performing a preoperative staging procedure? A pilot study.

Summary Background The aim of this pilot trial was to study the feasibility of sentinel node percutaneous preoperative gamma probe-guided biopsy as a valid preoperative method of assessment of nodal status compared to surgical sentinel lymph node biopsy. Material/Methods This prospective study enrolled 10 consecutive patients without evidence of axillary lymph node metastases at preoperative imaging. All patients underwent sentinel node occult lesion localization (SNOLL) using radiotracer intradermic injection that detected a “hot spot” corresponding to the sentinel node in all cases. Gamma probe over the skin detection with subsequent ultrasonographically guided needle biopsy of the sentinel node were performed. The percutaneous needle core histopathological diagnosis was compared to the results of the surgical biopsy. Results Preoperative sentinel node identification was successful in all patients. Conclusions The combination of preoperative gamma probe sentinel node detection and ultrasound-guided biopsy could represent a valid alternative to intraoperative sentinel node biopsy in clinically and ultrasonographically negative axillary nodes, resulting in shorter duration of surgery and lower intraoperative risks.

One-Step Nucleic Acid Amplification in Breast Cancer Sentinel Lymph Node: A Single Institutional Experience and a Short Review

Sentinel lymph node (SLN) examination is a standard in breast cancer patients, with several methods employed along its 20 years history, the last one represented by one-step nucleic acid amplification (OSNA). The latter is a intra-operative molecular assay searching for CK19 mRNA as a surrogate of metastatic cells. Our 3 years experience with OSNA (1122 patients) showed results overlapping those recorded in the same institution with a morphological evaluation (930 patients) of SLN. In detail, the data of OSNA were almost identical to those observed with standard post-operative procedure in terms of patients with positive SLN (30%) and micrometastatic/macrometastatic involvement of SLN (respectively, 38–45 and 62–55%). By contrast, when OSNA was compared to the standard intraoperatory procedure, it was superior in terms of accuracy, prompting the use of this molecular assay as a very valid, and reproducible for intra-operative evaluation of SLN. Further possibilities prompting the use of OSNA range from adhesion to quality control programs, saving of medical time, ability to predict, during surgery, additional nodal metastasis, and molecular bio-banking.

Follicular dendritic cell sarcoma with atypical features surrounding undescended testis: description of a rare case

Dendritic cell tumors are extremely rare neoplasms and occur both in nodal and extranodal sites. We report a case of an intra-abdominal follicular dendritic cell sarcoma (FDCS). The aim of this study is to describe histological, immunohistochemical, and ultrastructural features of FDCS in order to better define an abdominal mass with unusual immunophenotype and atypical clinical and radiological presentation.

Hypofractionation with simultaneous boost in breast cancer patients receiving adjuvant chemotherapy: A prospective evaluation of a case series and review of the literature

INTRODUCTION To evaluate acute toxicity and cosmetic outcomes of hypofractionated simultaneous integrated boost (SIB) as adjuvant treatment after breast-conserving surgery and adjuvant chemotherapy and to review the association of chemotherapy and short fractionation with boost. MATERIALS AND METHODS Patients presenting early-stage breast cancer were enrolled in a phase II trial. All patients received VMAT-SIB technique to the whole breast and tumor bed in 15 fractions, for a total dose of 40.5 and 48 Gy. Acute and late skin toxicities and breast pain were recorded. Cosmetic outcomes were also assessed as excellent/good or fair/poor. RESULTS Between August 2010 and December 2015, 787 consecutive patients were treated and had at least 2 year follow-up. A subset of 175 patients underwent adjuvant chemotherapy (median age of 55 years) and was analysed. The median follow up was 39 months (range 24-80). At the end of RT treatment, skin toxicity was G1 in 51.1% of patients, G2 in 9.7%. At 2 years of follow up, it was G1 in 13.5% of patients, no cases ≥ G2; cosmetic outcome was excellent in 63.5% and good in 36.5% of the patients. No significant difference compared to the patients without systemic therapy was observed. CONCLUSION Hypofractionated VMAT-SIB in patients who had undergone adjuvant systemic therapy was safe and well tolerated in terms of acute and early late settings and cosmesis. Our data confirmed the results of other studies published on the association of hypofractionation and chemotherapy or concomitant boost.