Use of tamoxifen in pT1a-pT1b, pN0 breast cancer.

PURPOSE: To evaluate if in low-risk breast cancer patients (pT1a-pT1b, pN0) tamoxifen can reduce local recurrence and improve survival. METHODS: Retrospectively 700 patients were analyzed. All patients were treated from 1980 to 2003 with conservative surgery plus radiotherapy at the University of Florence. No patients were treated with adjuvant chemotherapy. Tamoxifen was prescribed in 359 patients (51.3%). The crude probability of survival (or local recurrence) was estimated by using Kaplan-Meier method, and survival (or local recurrence) comparisons were carried out using Cox proportional hazard regression models. RESULTS: The univariate analysis for specific survival showed that only histological type and local recurrence were significant prognostic factors (log rank test: p=0.02 and p<0.0001, respectively). The Cox regression model by stepwise selection confirmed lobular histological type (p=0.008; HR: 3.83, 95% CI: 1.31-11.21) and local recurrence (p<0.001; HR: 9.05, 95% CI: 3.05-26.82) as independent prognostic factors for disease specific survival. For local disease free survival, multivariate analysis did not show any significant parameters. CONCLUSION: In our series tamoxifen did not seem to improve disease specific survival and local disease specific survival. The number of events in terms of death for cancer or in terms of local recurrence is too small in this group of patients. However, according to our results we suggest not to prescribe tamoxifen in patients affected by pT1a-pT1b, pN0 breast cancer.

Loco-regional recurrence in 2064 patients with breast cancer treated with mastectomy without adjuvant radiotherapy.

INTRODUCTION: We investigated the incidence of loco-regional recurrence in a sub-group of patients who underwent mastectomy without adjuvant radiotherapy to evaluate the effect of each specific clinical or pathological parameter that could be associated with a higher local relapse rate. PATIENTS AND METHODS: Two thousand and sixty-four patients were treated from January 1971 to December 2003 at the University of Florence. RESULTS: At the time of analysis 18.3% of patients (378/2064) had isolated loco-regional failures. Univariate analysis showed an association of borderline statistical significance with pathological tumour size. Elderly age at diagnosis had a low incidence of local recurrence but the results did not reach statistical significant. The number of positive axillary lymph node did not show any influence for local recurrence. CONCLUSION: In our series we noted a higher relapse rate only related to the pathological tumour size without any correlation with number of positive axillary nodes. Radiotherapy after mastectomy still remains controversial, but in our series the number of positive axillary lymph node did not seem enough to justify adjuvant treatment.

Adjuvant hypofractionated radiation therapy for breast cancer after conserving surgery.

AIMS: To evaluate the incidence of locoregional recurrence (LRR) and the cosmetic results in a group of patients with breast cancer treated with a hypofractionated schedule of adjuvant radiotherapy after conservative surgery. MATERIALS AND METHODS: In total, 539 patients with pTis-pT1-pT2 breast cancer underwent radiotherapy treatment after conservative surgery at the University of Florence and at the Pistoia Hospital. The dose delivered was 44 Gy (2.75 Gy daily fraction). The tumour bed boost (10 Gy) was given by electrons. RESULTS: At the time of the analysis, 1.8% of patients (10/539) had breast relapse. No patients developed nodal recurrence (supraclavicular, axillary and internal mammary nodes). The 3- and 5-year actuarial rates for LRR were 1.2% (+/- 0.5% standard error) and 2.1% (+/- 0.6% standard error), respectively. Considering the late toxicity, we found that 412 (76.4%) patients had grade 0 or grade 1 late toxicity, 113 patients (20.9%) had grade 2 late toxicity and 14 patients (2.5%) had grade 3 late toxicity. No patients developed grade 4 toxicity. CONCLUSION: This type of approach resulted in an effective treatment in terms of local control in patients with negative or one to three positive axillary nodes and negative surgical margins. Patients treated with a hypofractionated schedule showed very good cosmesis.

[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.

MOPP chemotherapy versus extended-field radiotherapy in the management of pathological stages I-IIA Hodgkin's disease.

In order to assess whether mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy (CT), which is less expensive and more easily available than radiotherapy (RT), is at least as effective as RT in terms of cure rate and has less iatrogenic damage, 89 consecutive patients with Hodgkin's disease (HD) (pathological stage I-IIA) were randomly allocated to receive mantle plus lumbar bar RT (36-45 Gy) or CT (six courses of MOPP). Forty-five patients were entered in the RT group and 44 in the CT group. The median follow-up was 60 months. Complete remission (CR) was obtained in all patients in the RT group and in 40 of 44 patients in the CT group. Overall survival (OS) and disease-free survival (DFS) were, respectively, 87.2% and 72.7% in the CT group and 93.5% and 74% in the RT group. Survival probability of relapsing patients was 76% for the patients in the RT group and 45% in the CT group. Treatment-related complications were more severe in the CT group as compared with the RT group.

Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathologic stage I-IIA Hodgkin's disease: eight-year update of an Italian prospective randomized study.

PURPOSE: To compare the effectiveness of chemotherapy (CHT) with extended-field radiotherapy (RT) in the treatment of early-stage Hodgkin's disease (ESHD), we report an 8-year updated analysis of a study in which treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) CHT was randomly compared with extended-field RT. PATIENTS AND METHODS: From August 1979 to December 1982, 89 adult patients with pathologic stage I-IIA Hodgkin's disease (HD) were randomly allocated to receive either RT with mantle field followed by periaortic irradiation (n = 45) or six monthly courses of MOPP CHT (n = 44). RESULTS: All patients in the RT arm and 40 of 44 in the CHT arm achieved complete remission. Twelve relapses occurred in each group. Eight patients treated with MOPP and two of the RT arm died of HD. Three other patients of the CHT group died because of a second cancer. With a median follow-up greater than 8 years, the overall survival rate is significantly higher in the RT than in the CHT group (93% v 56%; P less than .001), whereas the rates of freedom from progression and relapse-free survival (RFS) were similar in the two groups (76% v 64% and 70% v 71%, respectively). Of the 12 patients relapsing after RT, 11 (92%) achieved a second CR, compared with only six of the 12 (50%) in the MOPP group. Analysis of the response rate to salvage treatments showed that the type of relapse in the MOPP group was a prognostic indicator for the achievement of a second CR, whereas in the RT group, a second CR was obtained regardless of the characteristics of the relapses. At 80 months, the probability of survival of relapsing patients calculated from time of relapse was 85% and 15% in the RT and CHT groups, respectively (P = .02). CONCLUSION: We conclude that RT alone is the treatment of choice for adult patients with ESHD with favorable prognostic factors.

Tubular carcinoma of the breast: outcome and loco-regional recurrence in 307 patients.

PURPOSE: The aim of this study is to describe the University of Florence experience in evaluating clinical, pathologic and treatment factors as they are related to the outcome and loco-regional recurrence in patients with tubular breast carcinoma. MATERIAL AND METHODS: Three hundred and seven patients (median age 56.4 years, range 26-91 years) with histological verified tubular carcinoma of the breast were consecutively treated at University of Florence from 1976 to 2001. All patients were followed for a median of 8.4 years (range 3 months to 20 years). Thirty-seven women underwent mastectomy and 270 underwent breast conserving surgery. Positive axillary nodes were found in 15% of patients. Fifty-two patients did not undergo radiotherapy to whole breast after having breast conserving surgery. Tamoxifen was prescribed in 108 patients and chemotherapy in 21 patients, 15 out of 21 had positive axillary nodes. RESULTS: Cause specific survival was 99.6, 99.2 and 97.2% at 3, 5 and 10 years. Local recurrence rate was 1.9, 3.6 and 4.7% at 3, 5 and 10 years. Univariate statistical analysis was significant for specific survival and local recurrence for angiolymphatic invasion only (p=0.0004). CONCLUSIONS: In the absence of axillary disease and angiolymphatic invasion, conserving surgery with adjuvant radiotherapy is effective treatment of disease.

The management of elderly patients with T1-T2 breast cancer treated with or without radiotherapy.

AIM: The aim of the current study is to identify a subgroup of patients with breast cancer who have a low risk of local recurrence after conservative surgery in order to avoid radiotherapy treatment. METHODS: A group of 472 patients underwent conservative surgery without radiotherapy, and it was compared to a second group of 755 patients with similar characteristics, but who had received radiotherapy treatment (RT) after conservative surgery. RESULTS: Breast relapse's univariate analysis demonstrated statistical significance for the following factors: radiotherapy treatment, clinical stage, pathological stage, positive axillary nodes and tumour grading. Different results were obtained studying breast relapse. In the no-RT group breast relapse was 10.6% while in the irradiated group it was 3.4%. The breast relapse incidence decreases as the age of the patients increases especially over 75 years of age. CONCLUSIONS: In conclusion, there is clinical evidence of avoiding adjuvant radiotherapy for patients over 75 years with T1-T2 cancer treated with quadrantectomy with a clear excision margin.

Chemotherapy versus radiotherapy in early-stage Hodgkin's disease: evidence of a more difficult rescue for patients relapsed after chemotherapy.

Six cycles of mechloretamine, vincristine, procarbazine and prednisone (MOPP) chemotherapy were randomly compared with extended field radiotherapy (RT) in 89 adult patients with pathological stage I-II A Hodgkin's disease (HD). 45 patients received RT and 44 were treated with MOPP. Complete remission (CR) was obtained in all patients in the RT group and in 40 of 44 in the MOPP group. 12 patients relapsed in both groups. 10 out of 44 patients treated with MOPP died of HD, compared with only 2 in the RT group. 3 more patients died in the MOPP group following the occurrence of second cancers. 11 out of the 12 (96%) patients relapsing after RT achieved a second CR, compared with 6 out of the 12 (50%) patients relapsing after MOPP. Analysis of the response rate with salvage treatment, shows that, of the 12 patients who relapsed after MOPP, the pattern of relapse might predict the likelihood of achieving a second CR, whereas in the RT group a second CR was achieved regardless of the characteristics of relapse. Survival probability for relapsing patients at 80 months calculated from relapse was 85% in the RT group and 15% in the MOPP group (P = 0.02). With a median follow-up of more than 8 years, the overall survival of patients was significantly better for RT compared with MOPP; 93 and 56%, respectively (P < 0.001). On the basis of these results we conclude that, to date, RT alone remains the treatment of choice for adult patients with early-stage HD with favourable prognostic factors.

Uterine sarcoma: twenty-seven years of experience.

PURPOSE: A correlation of treatment for uterine sarcoma with outcome, prognostic importance of pathology, and clinical parameters. PATIENTS AND METHODS: One hundred forty-one patients (median age: 56 years, range: 19-85 years) with a histologically verified uterine sarcoma were identified from a database compiled at the Royal Marsden Hospital and the University of Florence between 1974 and 2001. Seventy-two patients had leiomyosarcoma, 42 had mixed müllerian tumors, 22 had endometrial stromal sarcoma, 1 hemangiopericytoma, 1 rhabdomyosarcoma, and 3 patients had unspecified sarcoma. According to FIGO classification, Stage I, II, III, and IV tumors were identified in 71, 13, 31, and 26 patients, respectively. RESULTS: At the time of analysis, 73.7% of patients were dead, and 26.3% were alive with a median survival of 2 years from initial diagnosis. Univariate analysis for cause-specific survival demonstrated statistical significance for histology (p = 0.02), grade (p = 0.003), stage (p = 0.007), and age (p = 0.02). Multivariate analysis demonstrated significant prognostic values for stage (p = 0.02) and histology (p = 0.05) only. Postoperative radiotherapy with a total dose higher than 50 Gy seems to be significant (p = 0.001) in reducing local recurrence. CONCLUSIONS: Our data favor treatment for Stages I, II, and III of uterine sarcoma with radical surgery plus radical dose irradiation comprising both external beam radiotherapy and brachytherapy.

Waldeyer's ring (WR) involvement in Hodgkin's disease.

Of 750 patients with stage I, II or III Hodgkin's disease, admitted to the University and Hospital Radiotherapy Divisions, Florence, between 1960 and 1981, 28 (3.7%) had involvement of Waldeyer's ring (WR). In 25 patients there was associated involvement of upper cervical nodes. Other factors associated with WR involvement were age over 55 years, lymphocyte predominant histological sub-type, uninvolved mediastinum, and size of involved upper cervical nodes greater than that of involved lower cervical nodes. These factors help to define indications for prophylactic irradiation of WR.

Neurological damage in patients irradiated twice on the spinal cord: a morphologic and electrophysiological study.

We reviewed the files of 950 patients treated for Hodgkin's disease since 1966 and were able to find five patients treated with radiochemotherapy and irradiated twice on volumes including a cord segment, at various time intervals, and surviving until now. Seven patients with comparable clinical and therapeutic features, but not reirradiated on the cord, were chosen as a control group and were examined with the same diagnostic procedures. The cumulative cord dose in the reirradiated patients was recalculated and ranged from 50 to 70 Gy. All these patients and the control cases were followed up for more than 10 years and presented no or only minor neurological symptoms. We compare the results of both magnetic resonance imaging (MRI) and electrophysiological studies (spinal and scalp recorded somatosensory evoked potentials--SEPs) in an attempt to define the characteristics of the subclinical damage present in these patients. While no cord abnormality was demonstrated with MRI, electrophysiological studies evidenced a clear difference between cases and controls, as far as the D10-P1 conduction time and SEPs average amplitude are concerned. Advantages and drawbacks of a wider use of electrophysiological methods in research work on cord radiation damage are presented, along with the possible implications of the results obtained for the understanding of the pathogenesis and of the dose dependence of radiation myelitis (RM).

Long-term nervous system damage from radiation of the spinal cord: an electrophysiological study.

A group of 13 patients suffering from Hodgkin's disease who had undergone chemotherapy and radiotherapy (above and below the diaphragm) approximately 10 years earlier was studied. The total chemotherapeutic dose was similar for all patients; the radiotherapy dose, however, was standard for 7 patients, while the other 6 received much higher dosages over limited regions of the spinal cord. Although most of these patients appeared normal both clinically and on magnetic resonance imaging, a neurophysiological study was performed to determine whether there was any involvement of the central or peripheral nervous system. Motor conduction velocity and sensory conduction velocity were measured in the lower limbs as well as spinal- and scalp-recorded somatosensory evoked potentials (SEPs) in response to stimulation of the posterior tibial and sural nerves at the ankle. In addition, motor evoked potentials were recorded from the upper and lower limbs during cortical stimulation. All neurophysiological data were normal in patients who had received a standard radiation dose, while most of those who had been exposed to higher doses showed altered cortical SEPs and a slowing of central conduction time (D10-P1). Thus even though they were asymptomatic, these patients appeared to have sustained CNS damage, mainly at the level of the spinal cord.

Mediastinal involvement in Hodgkin's disease: prognostic factors and distribution of intrathoracic adenopathies.

The files and the roentgenographic documentation of 624 patients affected by Hodgkin's disease have been reviewed. The presence and location of involved nodes in the different lymph node chains of the mediastinum have been determined and correlated with the distribution of the main anatomoclinic prognostic parameters of the disease. Feminine sex, histology of nodular sclerosis, presence of constitutional symptoms and age younger than 36 were found to be significantly more frequent in patients with mediastinal adenopathies than in patients with a normal mediastinum. Patients with mediastinal adenopathy at presentation were also more likely develop pulmonary involvement as first evidence of new manifestation of disease after the primary treatment. A different probability to be affected by disease was evident among the different lymph node groups in the mediastinum. The involvement of hilar nodes appeared to accompany a more advanced stage of disease and to favour the adjacent lung extension.

Stage I and II Hodgkin's disease presenting in infradiaphragmatic nodes.

Twenty patients with Hodgkin's disease limited to infradiaphragmatic (ID) nodes have been treated at the University and Hospital Radiotherapy Departments in Florence between 1960 and 1978. Clinicopathologic features and treatment modalities of these patients were reviewed and results compared with those of 2 similar series previously published by other authors. With respect to the patients with disease above the diaphragm, the ID presentation occurred more often in males in all the 3 reviewed series; a relative prevalence of the lymphocytic predominance histotype and of an older age was observed in 2 only of the 3 series; laparatomy seems unnecessary in lymphographic-negative patients. The analysis of therapeutic results suggests that inverted Y irradiation is a sufficient treatment when inguinal or lower iliac nodes only are affected; paraortic region and spleen involvement warrant a more radical program including the supradiaphragmatic irradiation or systemic chemotherapy.

Comparison of the conventional 'box technique' with two different 'conformal' beam arrangements for prostate cancer treatment.

PURPOSE: To quantify the possible advantages arising from the use of 'conformal' radiotherapy of localized prostate cancer, and to compare the dose distributions obtained with two different 'conformal' techniques. PATIENTS AND METHODS: Twelve patients with localized prostate cancer were enrolled in the study. For each patient, three techniques were planned: the standard 'box technique' (A), a four-fields 'conformal' technique (B), and a 6-fields conformal technique (C). For each of the 36 3D plans, dose-volume histograms (DVH) were obtained, along with the mean, maximum and minimum doses for the clinical and planning target volumes (CTV, PTV) for the rectum, the bladder, and the femoral heads. The resulting data were compared. RESULTS: On average, the standard technique resulted in the exposure of a significantly larger bladder volume to the higher doses; a similar, but less remarkable difference has been observed for the rectal volume. The coverage of the PTV appears to be significantly more homogeneous with the two conformal techniques. CONCLUSIONS: The results presented here add to the evidence available in the literature and suggest a possible advantage of both the conformal techniques over the standard 'box technique' for the treatment of localized prostate cancer. The 6-field conformal technique does not seem superior to the four field one.

Radical radiotherapy of localised prostate cancer: the relationship between radiation dose and survival.

PURPOSE: This retrospective study aims to define the effects of different radiation dose levels on survival, local control and toxicity in a series of 208 patients with localised prostate cancer consecutively treated with radical radiation therapy. PATIENTS AND METHODS: From 1982 through 1996, 365 patients with prostate cancer have been consecutively treated with radical radiotherapy in Florence (n = 306) and Arezzo (n = 59). The 208 cases treated until January 1994 with Stage B (125/208, 60%) and C (83/208, 40%) are the objects of the present study. The treatment was most often limited to the prostatic area (81%), using a four-field "box technique" and 25 MV photon beams, up to a total dose of 60-65 Gy (21% of the patients), of 66-69 Gy (26%) and of 70 Gy (53%); conventional fractionation was used (fractional dose: 2 Gy; five fractions/week). Hormonal therapy was also given to 39% of the cases. The possible relationship between dose, stage, grading and survival has been analysed. The survival figures and the types of relapse observed (prostatic, lymphnodal or "biochemical") have been analysed also according to the extent of the target volume and to the prostate-specific antigen (PSA) value at diagnosis, in the entire series or in selected subgroups. RESULTS: In the whole series and also after radiation alone, the patients with Stage B, with more differentiated tumours and those treated with higher doses to the prostate obtained significantly better survival results. Multivariate analysis confirmed that the dose level has an independent prognostic value. The use of a limited target volume did not produce an excess of pelvic lymphnodal failures. Among the patients more recently treated with radiation alone, the PSA level at diagnosis is strongly related with the risk of local and "biochemical" failure, and also with the relapse-free survival. Toxicity was acceptable, also for the patients treated with higher doses, but late treatment-related damage is more frequent in patients treated on larger volumes. CONCLUSION: The results of this retrospective analysis confirm the good results of small volume, high dose radiation therapy of prostatic cancer, even taking into account the possible biases due to the retrospective nature of the study, and the relevance of the PSA level at diagnosis to define the risk of local failure.