Synchronous bilateral testicular germ cell tumour: case report and review of the literature.

We report a case of a 30 years old male affected by synchronous bilateral germ cell tumor with a history of unilateral cryptorchidism; the patient underwent surgical treatment followed by adjuvant radiotherapy on paraaortic and iliac lymphnodes. Patients with synchronous tumors usually present with a higher stage disease in contrast to those with unilateral testicular carcinoma, yet the prognosis remains equally favorable.

Role of radiotherapy boost in women with ductal carcinoma in situ: a single-center experience in a series of 389 patients.

BACKGROUND: The use of adjuvant radiotherapy in ductal carcinoma in situ is accepted by most radiation oncologists worldwide; the role of a boost on the tumor bed is however more controversial. MATERIALS AND METHODS: We reviewed our Institute experience in DCIS treatment, focusing on main prognostic factors and impact of radiation boost on local relapse. A total of 389 patients treated between 1990 and 2007 were retrospectively analyzed. All patients received adjuvant radiotherapy after breast-conserving surgery for a median dose of 50 Gy; 190 patients (48.8%) received and additional radiation boost on the tumor bed. RESULTS: At a mean follow up of 7.7 years, we recorded 26 local recurrence (6.7%). Concerning local relapse-free survival, at Cox regression univariate analyses <1 mm surgical margins (p < 0.0001) and young age (p = 0.01) emerged as significant unfavorable prognostic factors. At multivariate analysis Cox regression model, surgical margins (p < 0.001) and radiation boost (p = 0.014) resulted as the significant independent predictors of recurrence. CONCLUSIONS: Our experience showed the negative prognostic impact of surgical margins <1 mm and the protective role of radiation boost on LR rate. Anyway, results from ongoing prospective Phase III studies are strongly necessary to better identify high-risk DCIS patients.

Neoadjuvant oxaliplatin and 5-fluorouracil with concurrent radiotherapy in patients with locally advanced rectal cancer: a single-institution experience.

PURPOSE: The aim of this study was to evaluate the rate of pathological response (PR), disease control and safety of neoadjuvant chemotherapy using oxaliplatin (OX) and 5-fluorouracil (5-FU) with concurrent radiotherapy for treating locally advanced rectal cancer. MATERIALS AND METHODS: Between November 2002 and December 2010, 90 patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) were retrospectively analysed. All patients underwent preoperative radiotherapy (45 Gy in 1.8-Gy fractions) with concurrent OX (80 mg/m(2) i.v., day 1) and a 120-h continuous infusion of 5-FU (1,000 mg/m(2) per day). Surgery was performed within 6 weeks after completion of CRT treatment. RESULTS: Complete pathological response was obtained in six patients (6.7%), and 39 (43.3%) had their disease downstaged. The median follow-up period was 4.7 years (6 months to 9 years). Local recurrence occurred in two patients (2.2%), one of whom developed also liver metastases. Distant metastases not associated with local relapse occurred in 23 (25.6%) patients. Overall (OS) and disease-free (DFS) survival were 62.9% and 52.8%, respectively. CRT was well tolerated, with only one grade 3 (1.2%) haematological toxicity (neutropaenia). CONCLUSIONS: Neoadjuvant systemic chemotherapy based on OX and 5-UC associated with radiotherapy is well tolerated, with good results in terms of pathological response, disease control and survival, in rectal cancer patients.

Treatment of invasive male breast cancer: a 40-year single-institution experience.

PURPOSE: We conducted a retrospective analysis to evaluate the management and outcome of invasive male breast cancer treated in a single-institution over a period of 40 years. MATERIALS AND METHODS: We reviewed the clinical and pathological features of 60 male patients affected by breast carcinoma treated at our Radiotherapy Unit between 1971 and 2011. Tumours were classified according to histological type and the updated 2010 TNM classification of malignant tumours. RESULTS: At a median follow-up of 8.9 [range, 0.6-20; standard deviation (SD), 4.98] years, 32 patients (53.3%) were alive and 16 patients died (26.7%) due to disease progression and 12 (20%) due to other causes. At univariate analysis for overall survival, pathological tumour size (p=0.031), histological subtype (p=0.013) and nodal status (p=0.006) emerged as significant predictors of death. At multivariate analysis, independent death predictors were advanced pathological tumour size (p=0.016), positive nodal status (p=0.003) and invasive cribriform histological type (p=0.0003). CONCLUSIONS: In consideration of the rarity of the disease, many issues are still being debated, and future collaborative studies are required. However, our experience confirms the prognostic role of greater pathological tumour size and positive nodal status as unfavourable features for survival in male breast cancer.

Normal tissues toxicities triggered by combined anti-angiogenic and radiation therapies: hurdles might be ahead.

BACKGROUND: Combined-modality therapy is a promising approach to improve the therapeutic index of radiotherapy. However, these improvements could come at the cost of increased toxicities. Clinical trials evaluating anti-tumour efficacy of bevacizumab combined with radiotherapy have encountered unexpected side effects. This study is the first systematic evaluation of normal tissue toxicity triggered by anti-angiogenic agents combined with radiation therapy in mice. METHODS: Effect of a mouse anti-VEGF antibody was monitored on acute toxicity studying radiation-induced intestinal ulceration (12 Gy TBI); on subacute toxicity using a model of oral mucositis (16.5 Gy); on late radiation injuries by monitoring lung fibrosis (bleomycin and 19 Gy). RESULTS: Combination of irradiation with anti-VEGF antibody enhanced intestinal damages with severe epithelial ulcerations, had no adverse impact on oral mucositis and dramatically worsened the fibrotic picture induced by bleomycin and irradiation to the lung. INTERPRETATION: These reports bring to light the important questions about safety and underscore the need for appropriate preclinical modelling of the impact on normal tissues of novel drug-radiation regimens. Our findings also highlight the complexity of anti-VEGF action, which could in defined conditions exert tissue-specific protection. The findings indicate that the combination of targeted drugs with radiotherapy should be approached with caution.

A benchmark study on 883 nasopharyngeal cancer patients treated in two Italian centres from 1977 to 2000. Part I: Evolving technical choices and survival.

PURPOSE: The authors sought to define treatment results according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades. MATERIALS AND METHODS: A total of 883 patients consecutively treated with radiotherapy between 1977 and 2000 at the Florence (FLO) and Brescia (IRA) Radiation Oncology centres were studied. Five-year overall (OS) and disease-specific (DSS) actuarial survival rates in the different pathological, clinical and therapeutic subgroups were calculated, along with the actuarial local-regional control (LRC) probability. RESULTS: At univariate analysis, survival and local control rates were significantly better in the more recent accrual periods and in the more favourable disease presentations; treatment-related parameters mainly affect LRC. At multivariate analysis, patient- and disease-related factors had a more evident prognostic effect than did therapeutic factors, although dose to the nasopharynx and treatment technique had a marginally significant impact on DSS and OS. CONCLUSIONS: Results of this benchmark study may be useful for understanding the development of new radio-therapy techniques for NPC, such as three-dimensional conformal radiotherapy (3D-CRT) and particularly intensity-modulated radiotherapy (IMRT).

A benchmark study on 883 nasopharyngeal cancer patients treated in two Italian centres from 1977 to 2000. Part II: Evolving technical choices and toxicity patterns.

PURPOSE: The authors sought to define toxicity patterns according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades. MATERIALS AND METHODS: A total of 883 patients consecutively treated with radiotherapy from 1977 to 2000 at the Florence (FLO) and Brescia (IRA) radiation oncology centres were studied. The crude incidence of late treatment toxicity in the different subgroups of patients was calculated and compared. RESULTS: Higher total and fractional doses and the "older" treatment techniques were related with an increased incidence of the main late effects of treatment. More recently treated patients experienced less treatment-related complications. CONCLUSIONS: Results of this benchmark study may have implications for understanding and developing new radiotherapy techniques, such as three-dimensional conformal radiotherapy (3D-CRT) and, in particular, intensity-modulated radiotherapy (IMRT) for NPC patients.

Pegylated liposomal doxorubicin (Caelyx®) and oral vinorelbine in first-line metastatic breast cancer patients previously treated with anthracyclines.

Doxorubicin is highly effective and widely used in breast cancer; however, its use is limited by cardiotoxicity related to its cumulative dose. In previous studies, pegylated liposomal doxorubicin (PLD) has shown an acceptable toxicity profile with minimal cardiotoxicity. Between June 2006 and October 2009, 27 metastatic breast cancer patients were treated with first-line PLD and vinorelbine at the University of Florence, Radiotherapy Unit. PLD (30 mg/m²) was administered on day 1, and oral vinorelbine (60 mg/m²) was administered on days 1 and 8 of a 4-week cycle. All patients were previously treated with anthracycline-based adjuvant chemotherapy. Median age was 52 years (range 38-69) and median time to metastasis was 78.5 months. There were no treatment interruptions or discontinuation for cardiac toxicity and no treatment-related deaths. Grade 3 hematological toxicity was observed in 18.6% of patients, and 3.7% had grade 3 non-hematological adverse events. With a median follow-up of 13.2 months (range 3-33), median response duration was 6.1 months, and median PFS was 5.3 months. The overall clinical benefit rate was 55.5%. Our experience adds to evidence supporting the activity and cardiac safety of PLD and vinorelbine in metastatic breast cancer patients previously treated with anthracycline-based adjuvant chemotherapy.

Use of doxorubicin plus cyclophosphamide followed by docetaxel as adjuvant chemotherapy for breast cancer.

We evaluated the feasibility and incidence of hematological toxicity in a series of 39 breast cancer patients treated at our institute with doxorubicin plus cyclophosphamide (AC) followed by docetaxel, using prophylactic G-CSF (pegfilgrastim). We prescribed G-CSF as secondary prophylaxis during the AC regimen and as primary prophylaxis during treatment with docetaxel. For the AC treatment, we recorded 6 cases of grade III (15.3%) and one case of grade IV (2.5%) neutropenia; we found one case of Grade IV anemia. For the docetaxel regimen, we registered one case of Grade IV (2.5%) neutropenia and three cases of Grade III leukopoenia without neutropenia. No patients experienced cardiac symptoms or baseline LVEF rate decrease. All patients concluded the programmed chemotherapy. Our experience shows the safety of docetaxel in combination with anthracyclines and the efficacy of prophylaxis with G-CSF in breast cancer adjuvant chemotherapy.

Concomitant adjuvant chemo-radiation therapy with anthracycline-based regimens in breast cancer: a single centre experience.

PURPOSE: This study was done to evaluate the toxicity related to concurrent radiotherapy and anthracycline (AC)-based chemotherapy in the adjuvant treatment of early breast cancer and to investigate the impact of treatment interruptions and the feasibility of this uncommon therapeutic approach. MATERIALS AND METHODS: From September 2002 to December 2007, 60 patients were treated at our Centre. The mean age at presentation was 48.5 (range 38-64) years. All patients underwent conservative surgery, and radiotherapy to the entire breast (mean dose 50 Gy; range 46-52 Gy). AC-based regimens consisted of four cycles of AC (doxorubicin plus cyclophosphamide) or four cycles of epirubicin (EPI) followed by four courses of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). RESULTS: Concomitant treatment caused acute skin G3 toxicity in 8.9% of patients and one case of G4 toxicity (1.7%). Concerning cardiac assessment, six of the 56 evaluable patients (10.7%) developed an asymptomatic decline of left ventricular ejection fraction >10% and <20% of the baseline value. Radiotherapy was temporarily stopped in 21.3% and chemotherapy in 57.1% of patients. CONCLUSIONS: In our experience, concomitant chemotherapy did not emerge as a significant factor in radiotherapy interruption. Moreover, no severe cardiac events were recorded.

Postmastectomy radiotherapy in breast cancer adjuvant treatment.

Radiotherapy (RT) plays an important role in the management of locally advanced breast cancer (BC). Postmastectomy RT has been shown to significantly reduce the risk of loco-regional failure and to improve disease free survival in high-risk women with BC. Many trials have shown a significant benefit in local control, disease-free and overall survival with the addition of RT for patients with stage II and III breast cancer. New perspectives are evaluating multiple biological variables that nowadays should be considered in clinical oncology for the prescription of postmastectomy radiation therapy. Tailored randomized trials are now ongoing to clarify the "grey zone" represented by the intermediate-risk group of patients (1-3 lymph nodes involved). We reviewed the major studies offered by literature with emphasis on the principal debated issues.

The impact of young age on breast cancer outcome.

AIMS: We conducted a retrospective analysis in order to evaluate the impact of age on women aged less than 35 years affected by breast cancer. MATERIALS AND METHODS: Between January 1972 and December 2006, 346 patients aged less than 35 years underwent adjuvant treatment at Florence University. The mean age of the patient population was 32 years (range 22-35): 76 patients were under 30 years old, the remaining were above 30 years old. RESULTS: In our series, 215 patients received adjuvant radiotherapy to whole breast after conservative surgery, 131 patients underwent mastectomy without subsequent radiation therapy and 323 patients had lymphadenectomy; 191 patients received adjuvant chemotherapy, 73 with anthracycline-containing regimen. With a median time of 2.5 years (range 6 months to 27.6 years) local relapses were observed in 67 cases (19.4%). At the multivariate analysis of local disease-free survival, ductal and ductal plus lobular histotypes, having more than 3 positive nodes, and age emerged as independent significant relapse predictors (p=0.018, p=0.0005, p=0.003 and p=0.024, respectively). For the DSS analysis, the median follow-up was 6.8 years (range 0.6-36.7 years). At the multivariate analysis, age (p=0.0038), positive nodes (p=0.0035) and distant metastases (p<0.0001) resulted to be independent death predictors. Patients younger than 30 had a worse prognosis. At the univariate analysis also local relapse resulted to be statistically significant (p=0.0004). CONCLUSIONS: Anthracycline-based chemotherapy seems to improve the outcome of these patients. However, there is an urgent need for tailored treatment investigations within the framework of randomized, controlled clinical trials.

The impact of young age on breast cancer outcome.

AIMS: We conducted a retrospective analysis in order to evaluate the impact of age on women aged less than 35 years affected by breast cancer. MATERIALS AND METHODS: Between January 1972 and December 2006, 346 patients aged less than 35 years underwent adjuvant treatment at Florence University. The mean age of the patient population was 32 years (range 22-35): 76 patients were under 30 years old, the remaining were above 30 years old. RESULTS: In our series, 215 patients received adjuvant radiotherapy to whole breast after conservative surgery, 131 patients underwent mastectomy without subsequent radiation therapy and 323 patients had lymphadenectomy; 191 patients received adjuvant chemotherapy, 73 with anthracycline-containing regimen. With a median time of 2.5 years (range 6 months to 27.6 years) local relapses were observed in 67 cases (19.4%). At the multivariate analysis of local disease-free survival, ductal and ductal plus lobular histotypes, having more than 3 positive nodes, and age emerged as independent significant relapse predictors (p = 0.018, p = 0.0005, p = 0.003 and p = 0.024, respectively). For the DSS analysis, the median follow-up was 6.8 years (range 0.6-36.7 years). At the multivariate analysis, age (p = 0.0038), positive nodes (p = 0.0035) and distant metastases (p < 0.0001) resulted to be independent death predictors. Patients younger than 30 had a worse prognosis. At the univariate analysis also local relapse resulted to be statistically significant (p = 0.0004). CONCLUSIONS: Anthracycline-based chemotherapy seems to improve the outcome of these patients. However, there is an urgent need for tailored treatment investigations within the framework of randomized, controlled clinical trials.

Adjuvant trastuzumab in breast cancer: experience from the University of Florence.

The objective of this study was to evaluate the efficacy and tolerability profile of sequential trastuzumab in the adjuvant treatment of non-metastatic breast cancer. We analyzed 94 patients with non-metastatic breast cancer who underwent postoperative treatment between November 2003 and December 2008 at the University of florence. All patients received one year of sequential trastuzumab after adjuvant chemotherapy. Cardiac monitoring in our study consisted of assessment of left ventricular ejection fraction (lVef) by echocardiography at baseline, after the completion of chemotherapy, then every 3 months during trastuzumab treatment and every 6 months thereafter. 91.6% of patients were alive without evidence of distant or local relapse, while 8.4% developed disease recurrence. The cumulative incidence of cardiotoxicity was 14.5%. In our experience trastuzumab given postoperatively with adjuvant chemotherapy was well tolerated and produced optimal clinical results in terms of disease-free survival.

Ischemic stroke during cisplatin-based chemotherapy for testicular germ cell tumor: case report and review of the literature.

Testicular germ-cell tumors are the most common solid tumor in young men, with an incidence peak between the ages of 20 and 35 years. Even if rare, arterial thromboembolism is a serious and possible complication during cisplatin-based chemotherapy in young patients. The strong association between rapid treatment and favorable outcome is well known. Oncologists need to recognize the symptoms and to alert a stroke unit as soon as possible. We report the management of a young patient affected by non seminomatous testicular neoplasm without cardiovascular risk factors who developed an ischemic stroke during cisplatin-based treatment. We also review the relevant literature.

Oral ibandronate in metastatic bone breast cancer: the Florence University experience and a review of the literature.

Ibandronate is an amino-bisphosphonate approved in metastatic breast cancer to reduce skeletal complications and to alleviate bone pain. we report our experience about the safety of oral ibandronate and review the literature.We treated 44 patients and administered 524 cycles of oral ibandronate (a single cycle was defined as a 50 mg capsule once daily for 28 days) with a median of 12 cycles (range 6-24). At a median follow-up of 18.5 months (range 6-28) the mean pain score decreased from 1.59 (SD+/-0.97) at baseline to 0.41 (SD+/-0.72) after 48 weeks of treatment. The mean analgesic score was 1.89 (SD+/-1.37) at baseline and 1.46 (SD+/-1.62) after 48 weeks of treatment. Ibandronate was generally well-tolerated; we had no Grade 3-4 adverse events. No patients had deterioration of renal function. No patients developed bisphosphonate-associated osteonecrosis of the jaw. Our experience confirmed that ibandronate may be a useful and safe co-analgesic to conventional treatments for bone pain in selected metastatic breast cancer patients.

Doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil as adjuvant chemotherapy in breast cancer.

This study evaluated whether doxorubicin and cyclophosphamide are superior to cyclophosphamide, methotrexate and 5-fluorouracil as adjuvant chemotherapy in breast cancer patients. Between July 1976 and December 2004, 1045 breast cancer patients received adjuvant chemotherapy at the Radiotherapy Unit of the University of florence. 927 were administered i.v. CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2) and 5-fluorouracil 600 mg/m(2) on days 1 and 8, repeated every 28 days for a total of six cycles) and 118 i.v. DC (doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) on day 1 repeated every 21 days for a total of four cycles). All patients underwent adjuvant radiotherapy as well. The survival analysis, stratified according to treatment, did not show any significant difference in metastasis occurrence between the two groups (log rank test p=0.42). According to multivariate analysis four parameters emerged as independent prognostic factors for distant metastases in patients treated with the Cmf regimen: pt (p=0.0005), number of positive axillary lymph nodes (p=<0.0001), tamoxifen use (p=0.0109) and local relapses (p=<0.0001). Only number of positive axillary lymph nodes and local relapses were significant predictors of metastases occurrence according to multivariate analysis in the DC group, 17 and p=0.028, respectively. No significant difference between the two regimens was observed with regards to number of involved nodes. DC and CMF produced similar outcome in breast cancer patients.

[Organ-confined prostate cancer: treatment with high doses of radioterapy (intensity modulated radiotherapy)]. / Cancer de próstata órgano-confinado: tratamiento con altas dosis de radioterapia (radioterapia de intensidad modulada).

PURPOSE: To report toxicity and local control in patients with localized prostate cancer, treated with high dose radiotherapy. MATERIALS AND METHODS: The records of 100 consecutive patients with clinically localized prostate cancer treated between june 2003 and may 2006 were reviewed. They received 80 Gy to the target volume with a biphasic technique (3DCRT + IMRT). The median pretreatment PSA was 9. The median follow-up time was 12 months. RESULTS: Eighteen (18%) developed acute Grade 2 rectal toxicity, and no patient experienced acute grade 3 or higher rectal symptoms. Forty-four (44%) developed acute Grade 2 urinary symptoms while 34% of the patients experienced no GU symptoms (Grade 0) during treatment. Three patients (3%) developed late rectal toxicity grade 2 and eight patients (8%) experienced late urinary toxicity grade 2; any patients experienced more severe symptoms. We recorded biochemical relapse in two patients, both had poor prognostic factors at initial diagnosis of prostate cancer. CONCLUSIONS: The data demonstrate the feasibility and safety of high dose radiotherapy for patients with localized prostate cancer and provide a proof that this method allow safe dose escalation with low severe toxicities to the normal tissues.