Cristina Piva

Radiation therapy in primary mediastinal B-cell lymphoma with positron emission tomography positivity after rituximab chemotherapy.

PURPOSE To investigate the role of radiation therapy (RT) in patients affected with primary mediastinal B-cell lymphoma (PMBCL) with residual (18)fluorodeoxyglucose positron emission tomography ((18)FDG-PET)-positive disease after rituximab chemotherapy (R-CT). METHODS AND MATERIALS Thirty-seven patients treated with R-CT and RT, all with (18)FDG-PET scan at diagnosis and before RT, were included. All (18)FDG-PET scans were reviewed, and responses were classified according to the Deauville 5-point scoring system. Outcomes measures were overall survival (OS) and progression-free survival (PFS), estimated for the whole cohort and for subgroups according to (18)FDG-PET score after R-CT. RESULTS The median follow-up time was 40.9 months. Three patients were assigned to Deauville score 1 (8.1%), 9 to score 2 (24.3%), 7 to score 3 (19%), 14 to score 4 (37.8%), and 4 to score 5 (10.8%). After RT, all patients with score 3-4 experienced a complete response (CR). Among patients with score 5, 1 was in CR (25%), 2 had persistent positivity (50%), and 1 showed progressive disease (25%). A total of 4 patients experienced progression or relapse: 1 of 33 (3%) with scores 1-4, and 3 of 4 (75%) with score 5. The 3-year OS and PFS of the whole cohort were 89.8% and 88.7%, respectively. OS was significantly different between scores 1-3 and scores 4-5 (100% vs 77% at 3 years, P<.05). Patients with a score of 5 had a significantly worse outcome than did all other patients (OS at 2 years, 33.3% vs 100%). CONCLUSIONS Approximately 50% of PMBCL patients show residual disease at (18)FDG-PET scan after R-CT. RT is able to convert to CR approximately 85% of these patients, but those with a Deauville score of 5 (10%) appear at high risk of progression and death, and they might be candidates for intensified programs.

Involved-Site Image-Guided Intensity Modulated Versus 3D Conformal Radiation Therapy in Early Stage Supradiaphragmatic Hodgkin Lymphoma

PURPOSE Image-guided intensity modulated radiation therapy (IG-IMRT) allows for margin reduction and highly conformal dose distribution, with consistent advantages in sparing of normal tissues. The purpose of this retrospective study was to compare involved-site IG-IMRT with involved-site 3D conformal RT (3D-CRT) in the treatment of early stage Hodgkin lymphoma (HL) involving the mediastinum, with efficacy and toxicity as primary clinical endpoints. METHODS AND MATERIALS We analyzed 90 stage IIA HL patients treated with either involved-site 3D-CRT or IG-IMRT between 2005 and 2012 in 2 different institutions. Inclusion criteria were favorable or unfavorable disease (according to European Organization for Research and Treatment of Cancer criteria), complete response after 3 to 4 cycles of an adriamycin- bleomycin-vinblastine-dacarbazine (ABVD) regimen plus 30 Gy as total radiation dose. Exclusion criteria were chemotherapy other than ABVD, partial response after ABVD, total radiation dose other than 30 Gy. Clinical endpoints were relapse-free survival (RFS) and acute toxicity. RESULTS Forty-nine patients were treated with 3D-CRT (54.4%) and 41 with IG-IMRT (45.6%). Median follow-up time was 54.2 months for 3D-CRT and 24.1 months for IG-IMRT. No differences in RFS were observed between the 2 groups, with 1 relapse each. Three-year RFS was 98.7% for 3D-CRT and 100% for IG-IMRT. Grade 2 toxicity events, mainly mucositis, were recorded in 32.7% of 3D-CRT patients (16 of 49) and in 9.8% of IG-IMRT patients (4 of 41). IG-IMRT was significantly associated with a lower incidence of grade 2 acute toxicity (P=.043). CONCLUSIONS RFS rates at 3 years were extremely high in both groups, albeit the median follow-up time is different. Acute tolerance profiles were better for IG-IMRT than for 3D-CRT. Our preliminary results support the clinical safety and efficacy of advanced RT planning and delivery techniques in patients affected with early stage HL, achieving complete response after ABVD-based chemotherapy.

Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

PURPOSE The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR(VMAT)-to-LAR(3D-CRT)) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). RESULTS The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. CONCLUSIONS In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by the different anatomical presentations, supporting an individualized approach.

Three-Dimensional Ultrasound-Based Image-Guided Hypofractionated Radiotherapy for Intermediate-Risk Prostate Cancer: Results of a Consecutive Case Series

External beam radiotherapy (EBRT) is a standard of care in the treatment of prostate cancer. Hypofractionation is a valid option either radiobiologically and logistically in this context. Image-guidance procedures are strongly needed to provide ballistic precision to radiation delivery. The Clarity platform allows for the acquisition of three-dimensional ultrasound scans (3D-US) to perform image-guided radiotherapy. We treated a consecutive series of intermediate-risk prostate cancer patients (according to NCCN stratification) with a hypofractionated schedule (70.2 Gy/26 fractions at 2.7 Gy/daily to the prostate gland excluding the seminal vesicles at 62.1 Gy) under 3D-US guidance with the Clarity platform. The 3-year biochemical-relapse-free survival, distant-metastases-free, cancer-specific and overall survival were 98.6% (CI: 91.1–99.6%), 98.6% (CI: 91.1–99.6%), 97.5% (CI: 94.5–99.1%), and 94.3% (CI: 90.4–96.7%), respectively. Maximum detected acute GU toxicity was G0 in 22 patients (29.7%), G1 in 30 (22.7%), G2 in 19 (25.6%), G3 in 3 (4%). Maximum detected acute GI toxicity at the end of EBRT was G0 in 42 patients (56.8%), G1 in 22 (29.7%), G2 in 9 (12.1%), G3 in 1 (1.4%). The 3-year actuarial rates of ≥ G2 late toxicities were 6.1% for genito-urinary and 8.9% for gastrointestinal. The whole image-guidance workflow resulted in being robust and reliable. EBRT delivered employing a hypofractionated schedule under 3D-US-based image guidance proved to be a safe and effective treatment approach with consistent biochemical control and a mild toxicity profile. Hence, it has been transferred into daily clinical practice in our Department.

Potential Benefit of Involved-Field Radiotherapy for Patients With Relapsed-Refractory Hodgkin's Lymphoma With Incomplete Response Before Autologous Stem Cell Transplantation

Micro‐Abstract We investigated the role of radiotherapy (RT) in 73 patients who received autologous stem cell transplantation (ASCT) for relapsed/refractory Hodgkin lymphoma by comparing patients who received peritransplantation RT with patients who received chemotherapy alone. In multivariate analysis RT had a marginal prognostic benefit in terms of overall survival, particularly for patients with limited and persistent disease before ASCT, thus suggesting a role for peritransplantation RT in these patients. Introduction: We investigated for a possible role for peritransplantation involved‐field radiotherapy (IFRT) by comparing patients who received IFRT before after autologous stem cell transplantation (ASCT) and patients who received salvage chemotherapy (CT) alone. Patients and Methods: We retrospectively evaluated 73 consecutive patients with Hodgkin lymphoma treated with ASCT between 2003 and 2014. Twenty‐one patients (28.8%) received peritransplantation radiotherapy. A Cox regression analysis (multivariate analysis; MVA) was performed to evaluate the prognostic role of any risk factor. Overall survival (OS) and progression‐free survival (PFS) were calculated from the date of ASCT. Response to CT and ASCT were evaluated with positron emission tomography (PET) scan. Results: Median follow‐up was 41 months (range, 1‐136 months). Overall, no significant difference appeared between patients who received IFRT and patients treated with CT alone; however, patients who were treated with IFRT had worse prognostic factors. In the MVA, advanced stage at relapse and persistent disease before ASCT (evident on PET scan [PET+]) were related to worse PFS and OS. In patients with limited stage disease at relapse and PET+, peritransplantation radiotherapy showed higher 3‐year OS rates (91.7% vs. 62.3%) and PFS rates (67.5% vs. 50%) compared with patients treated with CT alone, although this difference was not significant (P = .14 and P = .22, respectively). Conclusion: IFRT used before or after ASCT might partially compensate for worse prognostic factors among the overall population; subgroup analysis showed a trend for survival benefit at 3 years in patients with limited stage disease at relapse and PET+ before ASCT.

Interobserver variability in clinical target volume delineation for primary mediastinal B-cell lymphoma

PURPOSE The purpose of this study was to evaluate interobserver variability among radiation oncologists with experience in the field of lymphoma radiation therapy in the delineation of clinical target volume (CTV) in a challenging case of primary mediastinal B-cell lymphoma. METHODS AND MATERIALS Ten experienced radiation oncologists were invited to a 1-day contouring session. The case of a 56-year-old man with primary mediastinal B-cell lymphoma with complete metabolic response after chemotherapy was chosen as the sample for the study. A brief presentation of his clinical history was given, together with guidelines for contouring. The 10 CTVs obtained were then compared in terms of variation in total volume and in craniocaudal, laterolateral, and anteroposterior diameters. The CTV with the best Dice similarity coefficient (DSC) between the union of all 10 CTVs and the individual CTV was considered the reference CTV, and the DSC and the Hausdorff distance (HD) for each volume compared with the reference CTV were then calculated. RESULTS A significant variability was found in total volume (mean, 498.3 cm(3); range, 181.8-1003 cm(3)) and craniocaudal (median, 144.7 mm; range, 80.6-159 mm), laterolateral (median, 133.5 mm; range, 83.7-149.5 mm), and anteroposterior diameters (median, 136.2 mm; range, 84-150.5 mm). Analysis of the DSC and the HD showed a mean DSC of 0.53 (range, 0.31-0.74) and a mean HD of 6.4 cm (range, 1.8-14.8 cm). CONCLUSIONS Results of this study strongly indicate the need to develop and share appropriate contouring guidelines among experts and suggest the promotion of specific educational activities to improve radiation therapy quality in both clinical trials and routine clinical practice.

The role of radiation therapy in vulvar cancer: review of the current literature.

The purpose of this article is to discuss the current role of radiation therapy in vulvar cancer and especially to review the recent literature relative to the use of intensity-modulated radiotherapy (IMRT) in disease management. Owing to the low incidence of vulvar cancer, at present there are no available results of cooperative prospective trials. As evidenced in dosimetric and preliminary retrospective clinical studies, the use of IMRT has resulted in superior normal tissue sparing and lower rates of acute and chronic toxicities compared to previous studies that used conventional approaches. Data on long-term outcomes in these patients remain limited.

Olfactory neuroblastoma treated with minimally invasive surgery and adjuvant radiotherapy: a case report and review of the literature

Olfactory neuroblastoma (ON) is a rare tumour of the olfactory neuroepithelium that is characterized by a pattern of slow growth and local recurrences. Combination of surgery and radiotherapy, with or without chemotherapy, is considered to be the standard of care for primary site disease. Recent literature supports the view that endoscopic resection followed by adjuvant radiotherapy correlates with better outcome. In this short communication, we present a case report of olfactory neuroblastoma arising in the right nasal sinus in a 34-year-old male. This patient was treated with endoscopic resection and external beam radiotherapy to the right nasal sinus with intensity-modulated radiation therapy (IMRT) technique. After 2 years follow-up, the patient is free of tumour without any late effect related to therapies. We believe that, in such patients, a treatment strategy including endoscopic resection followed by adjuvant radiotherapy may be effective and feasible and should be considered the gold standard of care.

Extranodal Marginal Zone Lymphoma

Extranodal marginal zone lymphomas (EN-MZLs) comprise about 25 % of all non-Hodgkin lymphomas (NHL). The wide range of presentations of EN-MZL, involving virtually any organ, poses several challenges. The heterogeneity of the disease also explains the uncertainty and lack of consistency in radiotherapy approaches between centers and clinicians. EN-MZL often presents with localized/organ-confined disease, and RT is generally the primary curative modality. High local control rates can be achieved with relatively modest radiation doses, and local control often translates to cure.