Mattia Falchetto Osti

Long-Term Outcome after Multimodality Treatment for Stage III Thymic Tumors

BACKGROUND Surgery remains the cornerstone of therapy for thymic tumors, but the optimal treatment for advanced, infiltrative lesions is still controversial. The introduction of multimodality protocols has substantially modified survival and recurrence rate. We reviewed our 13-year prospective experience with multimodality treatment of stage III thymoma and thymic carcinoma. METHODS Since 1989 we have prospectively used a multimodality approach in 45 stage III thymic tumors. Sixteen patients (35%) had myasthenia gravis. Twenty-three patients (51%) had pure or predominantly cortical thymoma (group 1), 11 (24.5%) had well-differentiated thymic carcinoma (group 2), and 11 (24.5%) had thymic carcinoma (group 3). Tumors that were not considered radically resectable at preoperative workup underwent biopsy and induction chemotherapy (15 patients, 33%) followed by surgical resection; all patients were referred for adjuvant chemoradiotherapy. RESULTS No operative mortality was recorded; 1 treatment-related death during adjuvant chemotherapy was observed in group 1. Complete resection was feasible in 91% of patients in groups 1 and 2 and 82% in group 3. The overall 10-year survival was 78%. Ten-year survival for groups 1 and 2 was 90% and 85%, respectively; 8-year survival for group 3 was 56%. During follow-up, tumor recurrence was noted in 3 patients (13%) from group 1, 3 (27%) from group 2, and 3 (27%) from group 3. CONCLUSIONS Multimodality treatment with induction chemotherapy (when required) and adjuvant chemoradiotherapy offers encouraging results for stage III thymic tumors; the outcome is more favorable for cortical thymoma and well-differentiated thymic carcinoma.

The long‐term efficacy of conventional radiotherapy in patients with GH‐secreting pituitary adenomas

Objective  To assess the long‐term efficacy and safety of conventional radiotherapy (RT) in the control of acromegaly according to recent stringent criteria of cure.

Radiotherapy for nonfunctioning pituitary adenomas: from conventional to modern stereotactic radiation techniques

The initial management of nonfunctioning pituitary macroadenomas (NFAs) is usually surgery; however, a significant proportion of NFAs may require further treatment. Radiotherapy is currently used in patients with residual tumour and achieves excellent long-term control, but there are concerns about potential late toxicity. Stereotactic radiotherapy, both in the form of radiosurgery or fractionated stereotactic radiotherapy, has been developed as a more accurate technique of irradiation with more precise tumour localization and consequently a reduction in the volume of normal tissue, particularly the brain, irradiated to high radiation doses. A review of the literature suggests that new radiation techniques offer safe and effective treatment for recurrent or residual pituitary adenomas; however longer follow-up is necessary to confirm the excellent tumour control and the potential reduction of long-term radiation toxicity. Currently, radiotherapy has an important role in patients with residual or progressive disease after surgery. Patients with small or no residual tumours after surgery may generally continue on a policy of surveillance without immediate irradiation, in order to avoid the potential toxicity of treatment.

Fractionated stereotactic conformal radiotherapy for large benign skull base meningiomas

Purposeto assess the safety and efficacy of fractionated stereotactic radiotherapy (FSRT) for large skull base meningiomas.Methods and MaterialsFifty-two patients with large skull base meningiomas aged 34-74 years (median age 56 years) were treated with FSRT between June 2004 and August 2009. All patients received FSRT for residual or progressive meningiomas more than 4 centimeters in greatest dimension. The median GTV was 35.4 cm3 (range 24.1-94.9 cm3), and the median PTV was 47.6 cm3 (range 33.5-142.7 cm3). Treatment volumes were achieved with 5-8 noncoplanar beams shaped using a micromultileaf collimator (MLC). Treatment was delivered in 30 daily fractions over 6 weeks to a total dose of 50 Gy using 6 MV photons. Outcome was assessed prospectively.ResultsAt a median follow-up of 42 months (range 9-72 months) the 3-year and 5-year progression-free survival (PFS) rates were 96% and 93%, respectively, and survival was 100%. Three patients required further debulking surgery for progressive disease. Hypopituitarism was the most commonly reported late complication, with a new hormone pituitary deficit occurring in 10 (19%) of patients. Clinically significant late neurological toxicity was observed in 3 (5.5%) patients consisting of worsening of pre-existing cranial deficits.ConclusionFSRT as a high-precision technique of localized RT is suitable for the treatment of large skull base meningiomas. The local control is comparable to that reported following conventional external beam RT. Longer follow-up is required to assess long term efficacy and toxicity, particularly in terms of potential reduction of treatment-related late toxicity.

Surgical treatment of pituitary tumors in the elderly: Clinical outcome and long-term follow-up

Pituitary adenomas in the elderly represent an increasing proportion of pituitary tumors, making the surgical management of these patients of special importance. We therefore decided to review our experience with transsphenoidal surgery (TSS) in this age group, in order to better evaluate its efficacy, safety and outcome.A retrospective study was performed on 39 patients aged more than 70 years at the time of surgery (mean age 74.1 ± 2.9 years) and with a minimum follow-up duration of 4 years at the time of the study. Thirty-one had a nonfunctioning pituitary adenoma, 5 had a GH-secreting adenoma and 3 a macroprolactinoma, respectively. The commonest presenting symptom was visual deterioration (60%), whereas hypopituitarism were present in 41% of patients. All patients underwent TSS without any major peri- and post-operative complications. Visual fields improved in 74% of patients. Post-operative radiotherapy was performed in 17 patients with partial surgical resection and/or persistent hormonal hypersecretion, whereas 22 patients with subtotal or total surgical resection were treated by surgery only. Long-term follow-up (mean 9.1 ± 2.7 years) showed evidence for tumor regrowth in one irradiated (5.9%) and 3 non-irradiated patients (13.6%), respectively. A noticeable complication of radiotherapy was progressive hypopituitarism, which worsened or developed in 65% of patients.We conclude that TSS is safe and well tolerated even in elderly patients, with a low incidence of minor complications. The indications for post-operative radiotherapy in patients with incomplete tumor resection should be better defined.

MACOP-B and Involved-Field Radiotherapy Is an Effective and Safe Therapy for Primary Mediastinal Large B Cell Lymphoma

PURPOSE To report the clinical findings and long-term results of front-line, third-generation MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin) chemotherapy and mediastinal involved-field radiotherapy (IFRT) in 85 consecutive, previously untreated patients with primary mediastinal large B cell lymphoma (PMLBCL) diagnosed and managed at a single institution. METHODS AND MATERIALS Between 1991 and April 2004, 92 consecutive, untreated patients with PMLBCL were treated at our institution. The median age was 33 years (range, 15-61 years), 46 patients (50%) showed a mediastinal syndrome at onset; 52 patients (57%) showed a low/low-intermediate (0 to 1) and 40 patients (43%) an intermediate-high/high (2 to 3) International Prognostic Index (IPI) score. Eighty-five patients were treated with standard chemotherapy (MACOP-B), and 80 underwent mediastinal IFRT at a dose of 30-36 Gy. RESULTS After a MACOP-B regimen, the overall response rate was 87% and the partial response rate 9%. After chemotherapy, (67)Ga scintigraphy/positron emission tomography results were positive in 43 of 52 patients (83%), whereas after IFRT 11 of 52 patients (21%) remained positive (p < 0.0001). After a median follow-up of 81 months (range, 2-196 months), progression or relapse was observed in 15 of 84 patients (18%). The projected 5-year overall survival and progression-free survival rates were 87% and 81%, respectively. The 5-year overall survival and progression-free survival rates were better for patients with an IPI of 0 to 1 than for those with an IPI of 2 to 3 (96% vs. 73% [p = 0.002] and 90% vs. 67% [p = 0.007], respectively). CONCLUSIONS Combined-modality treatment with intensive chemotherapy plus mediastinal IFRT induces high response and lymphoma-free survival rates. Involved-field RT plays an important role in inducing negative results on (67)Ga scintigraphy/positron emission tomography in patients responsive to chemotherapy.

Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

PURPOSE Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. METHODS AND MATERIALS Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. RESULTS The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. CONCLUSIONS Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized studies are needed to compare HypoRT to conventional treatment.

Detection of colon cancer with 99mTc-labeled bombesin derivative (99mTc-leu13-BN1)

Breast, prostate, and lung cancer have been successfully detected with 99mTc bombesin (99mTc-leu13-BN1), the radiopharmaceutical that our group developed from synthesis to diagnostic trials. Overexpression of bombesin receptors (BNRs) in colon cancer is well known: the aim of this study was to assess whether or not colon cancer can be detected with a 99mTc-leu13-BN1 scan. Thirteen (13) patients, 7 of whom with known rectal cancer and 6 scheduled to undergo endoscopic removal of polyps for suspicion of colon cancer, were studied with a 99mTc-leu13-BN1 scan. Dynamic, single photon emission computed tomography, and whole-body scans were performed within 1 hour, before discharge of radioactivity from the liver into the duodenum. Sixteen (16) of 17 colorectal cancer locations were detected with a 99mTc-leu13-BN1 scan with 94.1% sensitivity. Six (6) lesions were benign: 1 Crohns disease, 1 polyp with mild dysplasia, 4 polyps with simple hyperplasia; 99mTc-leu13-BN1 scans were positive in two nontumoral lesions, Crohns disease, and mild dysplasia and true negative in 4: specificity was 67%. Of the 7 patients with known rectal cancer, 5, who underwent operations instead of radiation therapy, showed lymph-node invasion on 99mTc-leu13-BN1 scans. Operations confirmed the scintigraphic staging. 99mTc-leu13-BN1 is taken up by colon cancer. Scans are sensitive, although scarcely specific. 99mTc-leu13-BN1 allows for node-invasion detection.

Clinical Outcomes of Single Dose Stereotactic Radiotherapy for Lung Metastases

INTRODUCTION Stereotactic body radiation therapy is an emerging noninvasive technique for the treatment of oligometastatic cancer. The use of small numbers of large doses achieve a high percentage of local control. The aim of this study was to evaluate the efficacy and tolerability of SBRT for the treatment of lung metastases in a cohort of patients treated between 2008 and 2012 at our institution. PATIENTS AND METHODS A total of 66 patients with oligometastatic lung tumors (single pulmonary nodules in 40 patients; 61%) were included in the study. SBRT was performed with a stereotactic body frame and a 3-D conformal technique. Forty-nine central tumors received 23 Gy in a single fraction and 54 peripheral tumors received a dose of 30 Gy in a single fraction. The primary end point was local control; secondary end points were survival and toxicity. RESULTS Median follow-up was 15 months (range, 3-45 months). Local control rates at 1 and 2 years were 89.1% and 82.1%, overall survival rates were 76.4% and 31.2%, cancer-specific survival rates were 78.5% and 35.4%, and progression-free survival rates were 53.9% and 22%, respectively. Median survival time was 12 months, and median progression-free survival time was 10 months. Toxicity profiles were good, with 2 cases of Grade 3 toxicity (pneumonitis). CONCLUSION SBRT is an effective and safe local treatment option for patients with lung metastases, although it remains investigational; longer follow-up to confirm results is required.

Cytokines, Fatigue, and Cutaneous Erythema in Early Stage Breast Cancer Patients Receiving Adjuvant Radiation Therapy

We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1β, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1β, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.