[Curative radiotherapy in patients with anal cancer: clinical outcomes and prognostic factors in a single-institution experience]. / Risultati clinici e fattori prognostici dopo radioterapia curativa nei pazienti con cancro anale: l'esperienza di una singola istituzione.

PURPOSE: Our aim was to retrospectively analyse a series of patients with anal cancer treated with curative intent at a single institute in terms of survival and local disease control. MATERIALS AND METHODS: Forty-two patients with anal cancer were treated with primary radiotherapy with or without concurrent chemotherapy. The influence of the prognostic factors on overall (OS), disease-free (DFS), disease-specific (DSS), colostomy-free (CFS) and metastasis-free (MFS) survival was evaluated. RESULTS: Nine patients had stage I, 15 stage II, four stage IIIA and 14 stage IIIB disease. Tumour progression/ persistence occurred in five patients (12%). The 5-year OS, DSS, DFS, CFS and MFS were 72.7%, 84.2%, 85.7%, 81.1% and 87.1%, respectively. On univariate analysis, T stage emerged as highly significant for OS, DSS, CFS and DFS, whereas N status was a significant prognostic factor for DSS. On multivariate analysis, T stage was a significant prognostic factor for OS and CFS. CONCLUSIONS: Our data support the view that combined chemoradiation treatment of anal cancer is feasible and may provide survival benefits with an acceptable rate of adverse effects. We should consider T and N stages as important prognostic factors for survival.

External-beam radiotherapy and/or HDR brachytherapy in postoperative endometrial cancer patients: clinical outcomes and toxicity rates.

PURPOSE: The objectives of this study were to evaluate local disease control, overall survival (OS), disease-free survival (DFS) and local relapse-free survival (LRFS) in patients with endometrial cancer undergoing adjuvant vaginal brachytherapy (VBT )± external-beam radiotherapy (EBRT). MATERIALS AND METHODS: From September 2007 to February 2011, 40 patients with endometrial cancer were retrospectively analysed. Surgery consisted of total hysterectomy and bilateral salpingo-oophorectomy without node dissection (16 patients) or with bilateral pelvic node dissection (24 patients). The stage distribution was as follows: two IA, nine IB, 12 IC, five IIA, eight IIB, two IIIA and two IIIC. Thirty-four patients underwent EBRT and VBT. Six patients received VBT alone. RESULTS: Median follow-up was 26 months. The 5-year OS and DFS were 96.4% and 86.9%, respectively. No local recurrence was observed. Four patients presented distant disease (three had lung metastases and one had hepatic node metastases). Acute EBRT-related toxicities were seen in 15 (38%) patients. We recorded late toxicities in 14 patients (35%). There was no evidence of grade 3-4 toxicity. CONCLUSIONS: Adjuvant EBRT and/or VBT in patients with endometrial cancer showed good outcomes in terms of local disease control, with an acceptable toxicity profile.

Acute toxicity in 14 patients with locally advanced head and neck squamous cell carcinoma treated with concurrent cetuximab and radiotherapy.

PURPOSE: The authors report acute toxicity in 14 patients with locally advanced head and neck squamous cell carcinoma treated with radiotherapy and cetuximab. MATERIALS AND METHODS: Data collection was performed prospectively on patients treated from September 2007 to March 2009. Treatment consisted of 64.8-70 Gy radiotherapy in conventional fractions and cetuximab. RESULTS: Two out of 14 patients did not complete the planned combined treatment; radiotherapy was temporarily suspended in six other patients. Seven of 12 patients received cetuximab until the end of radiotherapy. Treatment breaks were principally due to severe acute cutaneous or mucous toxicity. Any grade acneiform rash occurred in all patients. In-field G3-4 cutaneous toxicity occurred in five (36%) patients and G3-4 mucous toxicity in seven (50%). One patient died of sepsis. CONCLUSIONS: In our experience, severe acute toxic reactions are common in patients treated with radiotherapy and concurrent cetuximab, resulting in frequent breaks or incomplete treatment with potential reduction in disease control.

Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide.

Epigenetic silencing of the O(6)-methylguanine-DNA-methyltransferase (MGMT) gene by promoter methylation is correlated with improved progression-free survival (PFS) and overall survival (OS) in adult patients with newly diagnosed glioblastoma multiforme (GBM) who receive alkylating agents. The aim of this study is to determine the correlation between MGMT and survival in elderly patients with GBM treated with radiotherapy (RT) and temozolomide (TMZ). Eighty-three patients aged 70 years or older with histologically confirmed GBM treated with RT plus TMZ between February 2005 and September 2009 were investigated in this study. The methylation status of the MGMT promoter was determined by polymerase chain reaction analysis. Median PFS and OS were 7.5 and 12.8 months, respectively. The MGMT promoter was methylated in 42 patients (50.6%) and unmethylated in 41 patients (49.4%). Median OS was 15.3 months in methylated patients and 10.2 months in unmethylated patients (P = 0.0001). Median PFS was 10.5 months in methylated tumors and 5.5 months in unmethylated tumors (P = 0.0001). On multivariate analysis MGMT methylation status emerged as the strongest independent prognostic factor for OS and PFS (P = 0.004 and P = 0.005, respectively). The results of the present study suggest that MGMT methylation status might be an important prognostic factor associated with better OS and PFS in elderly patients with GBM treated with RT and TMZ.

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.

Evaluation of therapeutic modalities in the control of Hodgkin's disease.

The results achieved in three different studies carried out on patients affected by Hodgkin's disease are discussed. In study No. 1, 58 patients with pathological Stage I-II were treated with only a "Mantle" field irradiation. The complete remission (CR) rate was 98% with an actuarial overall survival of 90%, and a median of follow-up of 80 months. Thirty-one percent of patients relapsed. In study No. 2, 42 patients were randomly allocated to receive only MOPP chemotherapy versus extended field irradiation; CR rate was 68 and 95%, respectively (p less than 0.05). The overall survival rate was 100% in the radiotherapy group and 82% in the MOPP group. No relapses have been observed in patients treated with MOPP. In study No. 3, 218 patients affected by advanced Stage HD were randomly treated with 6 cycles of MOPP chemotherapy versus 6 cycles of ABVD chemotherapy. In the MOPP group the CR rate, the relapse-free survival rate (RFS), and overall survival (OS) rates at 60 months were 77, 68, and 76% respectively, whereas, in the ABVD group the CR, the RFS, and OS rates at 60 months were 75, 77 and 80% respectively, (p less than 0.05). These data and statistical comparisons are analyzed.

Local recurrence in breast cancer after conservative surgery: timing of radiotherapy and sequencing of chemotherapy.

BACKGROUND: A randomized trial was conducted to determine (a) the role of radiotherapy and chemotherapy on local control and (b) to determine the timing of radiotherapy for early-stage breast cancer. MATERIALS AND METHODS: Five hundred and ninety patients were treated with both conservative surgery and radiotherapy (group A). The average time interval between surgery and radiation was 90 days for 452 patients and over 90 days for 138 patients. One hundred and ninety-four patients underwent adjuvant therapy based on CMF regimens (group B). RESULTS: Among 396 patients of group A, 8.1% had local failure; we observed 7.2% local recurrences in 363 patients who received therapy before 90 days and 18.2% in patients who received therapy after 90 days. Among patients of group B, 7.7% had local failure; for patients who underwent radiotherapy before 90 days, the local recurrence rate was 6.6%, compared with 12.3% for patients who underwent therapy more than 90 days after surgery. CONCLUSION: In patients who are eligible to receive chemotherapy, it is possible to administer radiotherapy after systemic treatment, while in patients who have to be treated with radiotherapy more then 90 days after breast surgery, chemotherapy can reduce the local failure rate.

MOPP treatment of resistant Hodgkin's disease following ABVD failure.

Fourteen patients with Hodgkin's disease resistant to ABVD were treated with MOPP chemotherapy (nitrogen mustard, vincristine, procarbazine, prednisone). Complete remission was obtained in 6 patients (43%). Four of the 6 complete responders are disease free after 5, 20, 23, 35 months. The actuarial median survival after MOPP of all patients is 20 months. These data confirm that there is no "cross-resistance" among the drugs included in the two schedules.

Secondary acute non lymphoid leukemia in patients treated for non Hodgkin's lymphoma: no risk of therapy-related ANLL after PROVECIP schedule.

The present study was undertaken to evaluate the frequency, characteristics and actuarial risk of secondary acute non lymphoid leukemia (s-ANLL) in 141 patients treated for non Hodgkin's lymphoma with different modalities. One hundred and twenty-four patients received chemotherapy according to PROVECIP protocol. Of these, 15 also received as induction treatment a local nodal irradiation and 33 an extended field radiotherapy. Seventeen out of 141 were treated by total body irradiation. Of these, 15 relapsed and received salvage chemotherapy. Sixteen of the 124 patients treated with PROVECIP also underwent different chemotherapeutic programs as salvage treatment. Of the entire population studied, 2 patients developed an s-ANLL, 45 and 63 months after diagnosis of NHL. The type of treatment significantly affected the occurrence of s-ANLL, since both leukemias occurred in patients treated with total body irradiation, given alone or followed by chemotherapy. The actuarial risk at 8 years was 5.24% in the whole group, whereas it greatly increased in the group of patients treated with total body irradiation (24%). Conversely, no risk was found in the group treated with PROVECIP, alone, with additional chemotherapy, or with associated local or extended field radiotherapy.

Bone marrow involvement at onset of Hodgkin's disease.

Bilateral trephine bone marrow biopsies of 370 patients with Hodgkin's disease first seen at the Institute of Hematology, University of Rome, between 1970 and 1981, revealed tumor involvement of the bone marrow in 18 cases. The histologic type was mixed cellularity in 7 cases, lymphocytic depletion in 4 cases, nodular sclerosis in 4 cases, and lymphocytic prevalence in 1 case. Anemia with less than 10 g/dl of hemoglobin was observed in 5 patients; white blood cells were less than 4.0 X 10(9)/liter in 2 patients; platelets were less than 12.0 X 10(9)/liter in 1 case; a pancytopenic condition was observed in only 1 case. B symptoms were present in 14 of the 18 patients. All patients who underwent laparosplenectomy presented spleen involvement, 4 also had liver involvement. All patients were treated with chemotherapy; MOPP regimen was employed in 11 cases, ABVD in 5 patients, and PROVECIP in 1 case. Of the 13 patients evaluable for therapeutic response, 11 achieved complete remission, with a median actuarial relapse-free survival of 15 months. The actuarial survival curve showed that 50% of all patients are projected alive at 47 months with a follow-up ranging from 1 to 109 months.

Technetium-99m tetrofosmin imaging in malignant lymphomas.

AIMS: To assess the utility of 99mTc tetrofosmin (TF) scintigraphy as a diagnostic modality in lymphomas. METHODS: Seventeen patients (14 with Hodgkin's disease and three with non-Hodgkin's lymphomas; age range, 10-59 years) were investigated. Planar and SPECT images of the supradiaphragmatic region (including neck and chest) were obtained. All patients were untreated at the time of the first scintigraphy. Follow-up scans after therapy were acquired in six patients (in five twice), so a total of 28 scintigraphic studies were performed. Mediastinal, pulmonary, cervical, supraclavicular and axillary activity was evaluated and results were compared in a blinded fashion with those of CT. RESULTS: TF imaging demonstrated pathological focal uptake at 38 sites (16 in the mediastinum, eight in the lungs, four in the axillae, eight in the supraclavicular region and two in the cervical region) in 16 of 17 untreated patients. CT identified 24 lesions (16 in the mediastinum, two in the lungs, two in the axillae, two in the supraclavicular and two in the cervical region) in 17 patients. Scintigraphy detected 22 of the 24 lesions demonstrated by CT and revealed 16 unknown tumor sites in 10 patients. The only negative pre-treatment scintigraphy result was found in a patient with axillary lymph node involvement. On the first post-treatment scintigrams there was a reduction in the number of visualized pathological sites (seven vs 16) in five of the six patients examined. The second follow-up study demonstrated only two lesions in two of the five patients examined. CONCLUSIONS: Our preliminary results indicate that TF imaging is effective in depicting supradiaphragmatic lymphoma lesions in untreated patients and suggest that serial scintigraphic studies may be suitable for monitoring response to treatment. However, larger series are needed to better define the possible role of TF scintigraphy in the follow-up of the response to therapy.

Stereotactic Irradiation of GH-Secreting Pituitary Adenomas.

Radiotherapy (RT) is often employed in patients with acromegaly refractory to medical and/or surgical interventions in order to prevent tumour regrowth and normalize elevated GH and IGF-I levels. It achieves tumour control and hormone normalization up to 90% and 70% of patients at 10-15 years. Despite the excellent tumour control, conventional RT is associated with a potential risk of developing late toxicity, especially hypopituitarism, and its role in the management of patients with GH-secreting pituitary adenomas remains a matter of debate. Stereotactic techniques have been developed with the aim to deliver more localized irradiation and minimize the long-term consequences of treatment, while improving its efficacy. Stereotactic irradiation can be given in a single dose as stereotactic radiosurgery (SRS) or in multiple doses as fractionated stereotactic radiotherapy (FSRT). We have reviewed the recent published literature on stereotactic techniques for GH-secreting pituitary tumors with the aim to define the efficacy and potential adverse effects of each of these techniques.

Subjective and objective measures of late genitourinary morbidity following hypofractionated radiotherapy in men with prostate cancer.

To value the late genitourinary (GU) morbidity in men treated with a hypofractionated radiotherapy regimen for prostate cancer. Patients with intermediate risk factors according to D'Amico's criteria were selected. The hypofractionated schedule consisted of 15 fractions of 3.63 Gy delivered three times per week for a total dose of 54.3 Gy. Significant changes in storage-symptoms were not found. A significant transient worsening in the score of late effects of normal tissue late effects normal tissue task force (LENT)-subjective, objective, management, analytic (SOMA) urinary-function domain was observed at 12 months with subsequent improvement at 28 months. The assessment of voiding-symptoms and maximum urinary flow rate (Qmax) showed that no significant difference was measurable at 12 and 28 months. For PVR, a transient increase at 12 months with a subsequent decrease at 28 months was measured. No significant increase in alpha-blockers usage and in the percentage of men with pathological nonintubated uroflowmetry (NIF) was observed at 12 and 28 months. Finally, patients did not perceive any clinical worsening in their quality of life (QoL) as attested by the International Prostate Symptom Score (IPSS)-QoL. Our study seems to suggest that our hypofractionated radiotherapy schedule for the treatment of prostate cancer is safe in terms of late urinary morbidity. Further study will be required to confirm our results.

Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma.

OBJECTIVES: The optimal treatment for elderly patients (age >70 years) with glioblastoma (GBM) remains controversial. We conducted a prospective trial in 43 consecutive elderly patients with GBM treated with hypofractionated radiotherapy (RT) followed by adjuvant temozolomide. PATIENTS AND METHODS: Forty-three patients 70 years of age or older with a newly diagnosed GBM and a Karnofsky performance status (KPS) > or = 60 were treated with hypofractionated RT (6 fractions of 5 Gy each for a total of 30 Gy over 2 weeks) followed by up to 12 cycles of adjuvant temozolomide (150-200 mg/m(2) for 5 days during each 28 day cycle). The HRQOL was assessed with the EORTC Quality of Life Questionnaire C30. The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS), toxicity and quality of life. RESULTS: The median OS was 9.3 months and the median PFS was 6.3 months. The 6 and 12 month survival rates were 86% and 35%, respectively. The 6 and 12 month PFS rates were 55% and 12%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.008). Neurological deterioration occurred during or after RT in 16% of patients and was resolved in most cases with the use of steroids. Grade 3-4 hematologic toxicity occurred in 28% of patients during the adjuvant chemotherapy treatment with temozolomide. The treatment had no negative effect on HRQOL, however, fatigue (P = 0.02) and constipation (P = 0.01) scales worsened over time. CONCLUSIONS: Hypofractionated RT followed by temozolomide may provide survival benefit maintaining a good quality of life in elderly patients with GBM. It may represent a reasonable therapeutic approach especially in patients with less favourably prognostic factors.

Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients.

OBJECTIVES: The optimal treatment for elderly patients (age > 70 years) with glioblastoma remains controversial. We conducted a prospective trial in 32 consecutive elderly patients with glioblastoma who underwent surgery followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide. PATIENTS AND METHODS: 32 patients 70 years of age or older with a newly diagnosed glioblastoma and a Karnofsky performance status (KPS) > or = 70 were treated with RT (daily fractions of 2 Gy for a total of 60 Gy) plus temozolomide at the dose of 75 mg/m(2) per day followed by six cycles of adjuvant temozolomide (150-200 mg/m(2) for 5 days during each 28-day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and toxicity. RESULTS: The median OS was 10.6 months and the median PFS was 7 months. The 6-month and 12-month survival rates were 91% and 37%, respectively. The 6-month and 12-month PFS rates were 56% and 16%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.01). Adverse effects were mainly represented by neurotoxicity (40%), which resolved in most cases with the use of steroids, and Grade 3-4 hematologic toxicity in 28% of patients. Chemotherapy was stopped in 2 patients, delayed in 9 patients and reduced in 4 patients. CONCLUSIONS: Standard RT plus concomitant and adjuvant temozolomide is a feasible treatment for elderly patients with newly diagnosed glioblastoma who present with good prognostic factors.

[Radiation pneumopathy. Our experience in the treatment of Hodgkin's disease with mantle-shaped field radiotherapy]. / Pneumopatia da radiazioni. Nostra esperienza nel trattamento del morbo di Hodgkin con campo sagomato a mantellina.

The literature of the radiation pneumonitis is reviewed from the standpoint of the pathogenesis, histopathology and dependent parameters of the disease. A series of 125 patients treated with mantle fields for Hodgkin's disease between 1972/80 is studied. The radiation pneumonitis developed radiologically in 28 patients (22,4%); in 20 (72%) was asymptomatic. The incidence of pneumonitis against the time of onset of the disease, reveals a peak about the first three months after the end of radiotherapy. No significative variations of incidence of disease are seen in two groups of patients treated respectively with and without chemotherapy (20% and 26%). Frequency diagrams of pneumonitis as a function of the calculate values of the dose for TD, rets, TDF, show a significant correlation with the ranges of doses expressed in TDF.

[Nuclear magnetic resonance in oncologic radiotherapy]. / La risonanza magnetica nella radioterapia oncologica.

The possibilities of utilizing Nuclear Magnetic Resonance in Radiation Oncology are examined, on the basis of information provided by spectroscopy (MRS), studies on the tissues characterization of tumors, and preliminary practical application of imaging (MRI) to radiation therapy. MRS affords information on the bioenergetics of the tumor cells, and on the biochemical changes induced by ionizing radiation; further, some results of clinical importance were obtained in "monitoring" tumor response to radiation therapy and chemotherapy. Tissue characterization of normal tissues and of tumor is analyzed; technical factors, morphological elements, and structural elements are considered. Morphological elements include anatomical recognition, clinical and radiological evaluation, appraisal of the peritumoral tissues, and analysis of inhomogeneities. Among structural elements are considered some methods suitable to achieve a full evaluation of tissue characterization of tumors, on the basis of an appropriate employment of sequence parameters. Practical application of MRI on radiotherapy of tumors comprises staging procedures, contribution to the selection of differentiated radiation volumes for radiotherapy planning, and new data on the evaluation of biological effects of ionizing radiation on normal tissues of patients.

[Role of radiotherapy in the treatment of seminoma of the testis]. / Ruolo della radioterapia nel trattamento del seminoma del testicolo.

From 1965 through 1988, 113 patients affected with testicular seminoma were treated at the Dept. of Radiotherapy, University "La Sapienza", Rome, Italy. Mean age of the patients was 38 years; in 70 cases tumor developed in the right testis and in 43 in the left one. In 9 patients underlying cryptorchidism was observed. All cases underwent radical orchiectomy. Histology diagnosed anaplastic seminoma in 5 cases and pure seminoma in all the other patients. Structures were involved in 7 cases. Eighty-four patients were in stage I, 20 in stage IIA, 4 in IIB, 4 in IIIA, and 1 in stage IIIB. All patients staged as I and IIA were treated with exclusive radiotherapy on paraaortic lymph nodes and inguinal and iliac lymph nodes of the involved sites (total doses: 28-35 Gy in stage I and 34-40 Gy in stage IIA). Before 1970 these patients underwent prophylactic irradiation of mediastinum and of left supraclavicular lymph nodes (total dose: 25-28 Gy). Patients in stage IIB were administered subdiaphragmatic lymph nodes irradiation with inverted-Y field (total dose: 36-45 Gy). Two cases were irradiated also on mediastinum and left supraclavicular lymph nodes, and 2 received two cycles of polychemotherapy (PVB) before irradiation. Patients in stage IIIA underwent sub-/supra-diaphragmatic irradiation (total dose: 40-45 Gy, and 40-42 Gy). The case in stage IIIB underwent palliation chemotherapy and local irradiation. All cases in stages I, IIA and IIB obtained complete remission. Three cases of the 4 in stage IIIA obtained complete remission (75%), while 1 (25%) progressed and died 8 months after diagnosis; the only case in stage IIIB progressed and died after 7 months of follow-up. Two cases in stage I recurred (2.4%), 1 in the mediastinum and 1 in the left supraclavicular lymph nodes. Both were cured with salvage radiation therapy. Toxicity related to treatment was low. Two cases in stage I developed secondary malignant neoplasms, at 4 and 34 months of follow-up, respectively.