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Although there is still no standard treatment for recurrent glioblastoma multiforme (rGBM), re-irradiation could be a therapeutic option. We retrospectively evaluated the efficacy and safety of re-irradiation using helical TomoTherapy (HT) with a simultaneous integrated boost (SIB) technique in patients with rGBM. 24 patients with rGBM underwent HT-SIB. A total dose of 20 Gy was prescribed to the Flair (fluid-attenuated inversion recovery) planning tumor volume (PTV) and 25 Gy to the PTV-boost (T1 MRI contrast enhanced area) in 5 daily fractions to the isodose of 67% (maximum dose within the PTV-boost was 37.5 Gy). Toxicity was evaluated by converting the 3D-dose distribution to the equivalent dose in 2 Gy fractions on a voxel-by-voxel basis. Median follow-up after re-irradiation was 27.8 months (range 1.6-88.5 months). Median progression-free survival (PFS) was 4 months (95% CI 2.0-7.9 months), while 6-month PFS was 41.7% (95% CI 22.2-60.1 months). Median overall survival following re-irradiation was 10.7 months (95% CI 7.4-16.1 months). There were no cases of re-operation due to early or late toxicity. Our preliminary results suggest that helical TomoTherapy with the proposed SIB technique is a safe and feasible treatment option for patients with rGBM, including those large disease volumes, reducing toxicity.

Background: Concurrent chemotherapy and radiation using conventional fractionation is the standard treatment for inoperable, locally advanced non-small-cell lung cancer (NSCLC). We tested accelerated hypofractionated radiotherapy (AHR) and chemotherapy for the treatment of locally advanced NSCLC., Methods: Eligible patients with locally advanced NSCLC were treated with induction chemotherapy (cisplatin and docetaxel), followed by AHR using tomotherapy and consolidation chemotherapy. The prescribed doses were 30 Gy/5 daily fractions at the reference isodose (60-70%) to the tumor, and 25 Gy/5 daily fractions to the clinically involved lymph nodes. The primary end-point was response rate (RR); the secondary end-points were acute and late side-effects, local progression-free survival (PFS), metastasis-free survival (MFS) and overall survival (OS). This trial closed before the first planned interim analysis due to poor accrual., Results: From January 2009 to January 2012, 17 of the 23 enrolled patients were evaluable. Treatment yielded an overall RR of 82%. Median follow-up was 87 months (range: 6-87), local PFS was 19.8 months (95% CI 9.7 - not reached), MFS was 9.7 months (95% CI 5.8-46.0) and OS was 23 months (95% CI 8.4-48.4). 70% of patients experienced acute G4 neutropenia, 24% G4 leukopenia, 24% G3 paresthesia, 4% G3 cardiac arrythmia, 4% underwent death after chemotherapy. Late toxicity was represented by 24% dyspnea G3., Conclusions: AHR combined with chemotherapy is feasible with no severe side-effects, and it appears highly acceptable by patients., Trial Registration: This study is registered with the EudractCT registration 2008-006525-14 . Registered on 9 December 2008.

The potential of a spheroid tumor model composed of cells in different proliferative and metabolic states for the development of new anticancer strategies has been amply demonstrated. However, there is little or no information in the literature on the problems of reproducibility of data originating from experiments using 3D models. Our analyses, carried out using a novel open source software capable of performing an automatic image analysis of 3D tumor colonies, showed that a number of morphology parameters affect the response of large spheroids to treatment. In particular, we found that both spheroid volume and shape may be a source of variability. We also compared some commercially available viability assays specifically designed for 3D models. In conclusion, our data indicate the need for a pre-selection of tumor spheroids of homogeneous volume and shape to reduce data variability to a minimum before use in a cytotoxicity test. In addition, we identified and validated a cytotoxicity test capable of providing meaningful data on the damage induced in large tumor spheroids of up to diameter in 650 μm by different kinds of treatments.

Although combination chemotherapy and radiotherapy have become the standard of care in numerous tumors, the mechanisms of interaction are often still unclear. The purpose of this study was to analyze the efficacy of radiation treatment and cisplatin sequences and to investigate their mechanisms of interaction. Three melanoma cell lines were used to evaluate in vitro radiation-induced cytotoxicity before and after cisplatin treatment. Expression levels of a panel of genes were determined by real-time RT-PCR. Cytotoxic effect was evaluated by flow cytometry analysis and Comet assay. We also used normal human dermal fibroblasts (HUDE) to evaluate the cytotoxicity of the two treatments by clonogenic assay. Radiation and cisplatin used singly were not particularly effective in reducing proliferation in melanoma cells. Conversely, radiation treatment followed by cisplatin showed a strong synergistic interaction in all cell lines, with a ratio index ranging from 16 to >100. The synergistic effect was accompanied by apoptosis induction (up to 40%) and an increase in the percentage of comet-shaped nucleoids from 85% to 99%. In parallel, our results also showed that radiation treatment of HUDE fibroblasts followed by cisplatin only induced weak cytotoxicity. Our findings highlight the efficacy of the sequence radiation → cisplatin in reducing cell proliferation and in inducing apoptosis in melanoma cell lines. This sequence also modulated a network of proteins involved in DNA damage repair., (© 2014 Wiley Periodicals, Inc.)

Background: Although two-dimensional (2-D) monolayer cell cultures provide important information on basic tumor biology and radiobiology, they are not representative of the complexity of three-dimensional (3-D) solid tumors. In particular, new models reproducing clinical conditions as closely as possible are needed for radiobiological studies to provide information that can be translated from bench to bedside., Methods: We developed a novel system for the irradiation, under sterile conditions, of 3-D tumor spheroids, the in vitro model considered as a bridge between the complex architectural organization of in vivo tumors and the very simple one of in vitro monolayer cell cultures. The system exploits the same equipment as that used for patient treatments, without the need for dedicated and highly expensive instruments. To mimic the passage of radiation beams through human tissues before they reach the target tumor mass, 96-multiwell plates containing the multicellular tumor spheroids (MCTS) are inserted into a custom-built phantom made of plexiglass, the material most similar to water, the main component of human tissue., Results: The system was used to irradiate CAEP- and A549-derived MCTS, pre-treated or not with 20 μM cisplatin, with a dose of 20 Gy delivered in one session. We also tested the same treatment schemes on monolayer CAEP and A549 cells. Our preliminary results indicated a significant increment in radiotoxicity 20 days after the end of irradiation in the CAEP spheroids pre-treated with cisplatin compared to those treated with cisplatin or irradiation alone. Conversely, the effect of the radio- chemotherapy combination in A549-derived MCTS was similar to that induced by cisplatin or irradiation alone. Finally, the 20 Gy dose did not affect cell survival in monolayer CAEP and A549 cells, whereas cisplatin or cisplatin plus radiation caused 100% cell death, regardless of the type of cell line used., Conclusions: We set up a system for the irradiation, under sterile conditions, of tumor cells grown in 3-D which allows for the use of the same dose intensities and schedules utilized in clinical practice. This irradiation system, coupled with 3-D cell cultures, has the potential to generate information that could be used to individually tailor radiotherapy.

Background/aims: The aim of this prospective phase II study was to evaluate the effect of neoadjuvant GEMOX plus helical tomotherapy on the resectability of locally advanced pancreatic cancer., Methodology: Between November 2004 and July 2008, 33 enrolled patients received gemcitabine (GEM) 1000 mg/m2 on day 1, and oxaliplatin (OX) 100 mg/m2 on day 2, every two weeks for 3-4 cycles. This was followed by radiotherapy (25 Gy, 5 fractions), 15 days after completion of GEMOX. Patients then received a further 3-4 cycles of GEMOX, underwent restaging and were evaluated for surgery. Potentially resectable patients were submitted to surgery, while unresectable responders received further GEMOX and radiotherapy., Results: Toxicity to GEMOX was similar to that reported elsewhere and radiotherapy was also well tolerated. After treatment, one patient achieved a complete response, 14 had a partial response, 11 showed a stable disease, 6 progressed, and one was not evaluable. Eight patients (24%) underwent surgical laparotomy (7 radical pancreatic resections and one explorative laparotomy)., Conclusions: Our study shows the feasibility and potential efficacy of the GEMOX plus helical tomotherapy regimen in unresectable locally advanced pancreatic cancer.

Aims and Background: The stomach is the most common site of primary extranodal non-Hodgkin's lymphoma (NHL) and no agreement has been reached so far on the best therapeutic approach. The main objects of this study were to report the long-term results and to evaluate the importance of some possible prognostic factors in a large series of patients. NHL was considered primary gastric if the main symptoms at presentation were those of gastric disease., Methods and Study Design: We analyzed 252 consecutive patients treated between 1980 and 1993 in five hospitals in north-east Italy. According to the Working Formulation, 98 patients had low grade lymphoma, 59 intermediate grade (D to F), 81 G or high grade and 14 were not classified. The patients were divided into two groups: one including patients with limited disease (localized to the stomach or perigastric lymph nodes: 165 patients) and one including those with advanced disease (87 patients). The treatment consisted of surgery, chemotherapy, radiotherapy or combinations of these. Sixteen patients received only supportive therapy., Results: The five-year overall survival was 65.4%: 80.3% for patients with limited disease and 36.7% for those with advanced disease (P < 0.0001). Among the limited disease patients the five-year survival was 84.4% for those treated with gastrectomy alone and 88.7% for those who received also adjuvant chemotherapy (P = 0.11). However, while chemotherapy did not improve survival in low grade NHL, it seemed to produce a better survival in the intermediate and high grade groups (P = 0.06). Twelve patients were treated with primary chemotherapy and the five-year survival was 71.2%. In multivariate regression analysis the most important variable for overall survival was surgery for the whole group of 252 patients (P < 0.0001), while it was age for the group with limited disease (P = 0.0008)., Conclusions: Surgery alone can be curative for most patients with gastric lymphoma limited to the stomach or to the perigastric lymph nodes; surgery followed by chemotherapy seems to produce better results than surgery alone in intermediate and high grade lymphomas. Also a non-surgical approach with first-line chemotherapy is associated with a high rate of complete remissions and five-year survival. In advanced disease the five-year survival is similar to that of nodal NHL.

Introduction: We report our personal experience with the treatment of tonsillar cancers at the Otorhinolaryngology-Radiotherapy Department of Umberto I Hospital, Mestre, Italy. The results were analyzed by tumor site and stage, lymph node involvement, treatment type and patient age., Material and Methods: January, 1987, through December, 1995, we treated a hundred and 25 patients with carcinoma of the tonsil and tonsillar region. Most patients were men (M:F = 4:1), with a mean age of 61.9 years (range: 38-87). The lesions were staged at physical examination, chest radiography, bone scintigraphy. US of the liver and neck, CT and/or MRI of the tonsillar region and neck. Eleven patients were in stage I (8.8%), 26 in stage II (20.8%), 31 in stage III (24.8%) and 57 in stage IV (45.6%). Forty-one patients were submitted to tonsillectomy and more/less massive neck dissection: surgery was not radical-in 14 of them. All patients received gamma-photon radiotherapy with a cobalt unit: the minimum dose was 50 Gy after radical surgery and 60 Gy for exclusive irradiation and after nonradical surgery. The hemiblock field technique was always used with the conventional fractionation (2 Gy/day. 1 fraction/day, 5 fractions/week); the treatment was planned with the Theraplan V05-B method on CT scans. When the tolerance dose was reached, the spinal cord was shielded and the dose compensated with 9 MeV electrons. The treatment was discontinued only when needed, and never for more than 7-10 days., Results: The overall 5-year survival and the 5-year disease-free survival rates were 28% and 45%, respectively; the overall 5-year cause-specific survival rate was 39%. Disease-free survival was 81% in stage I, 52.7% in stage II, 44.2% in stage III and 35.8% in stage IV (p = .005). The 5-year disease-free survival for the patients receiving surgery and irradiation was 62.1%, versus 38.3% for irradiation alone; the rate was 37.6% when neck nodes were involved (N+). One hundred and two patients achieved complete remission (CR), while the other 23 had partial remission (PR). Twenty-eight CR patients recurred; the most common cause of death was failure in primary tumor local control. There were no complications during or after treatment. Secondary lesions were found in 13 patients (10.1%)., Conclusions: Irradiation alone yields fairly good results in early tonsil carcinoma, while the surgery-irradiation combination should be preferred in large tumors. Better results are expected from kinetic and conformal irradiation techniques with 3D calculations on CT and MR images, which should permit to deliver high doses to strictly targeted areas and to reduce side-effects. Other improvements are expected from new combination therapies.

Rendu-Weber-Osler disease is a rare autosomic disorder. Its most common symptom is epistaxis with transitory periods of remission and of ingravescent exacerbation compromising normal daily activities and forcing the patient to give up his normal life-style for prolonged periods of time. Often it proves difficult to control the recurrent epistaxis and the treatments available today are not always totally satisfactory. The authors present the results obtained using endonasal brachytherapy in 8 patients (13 treatments) epistaxis stemming from previously diagnosed Rendu-Weber-Osler disease. Brachytherapy employs thin plastic tubes, positioned in the nostril with the heaviest epistaxis. These tubes are then filled with Iridum192. The total dose, prescribed against the reference isodose, strictly adjacent to the nasal fossae mucosa, was 30 Gy over a period ranging from two to four days (average 2.5 days). Four patients required a second treatment to the controlateral nostril as the symptoms returned after a period ranging from 36 to 60 months (average 47.1 months). Only one patient required a second treatment in the same nostril 9 years later. The episodes of epistaxis were scored by symptom severity on a scale from 0 to 5. Of the 13 treatments administered (mono and bilateral treatments), 12 can be considered satisfactory as the epistaxis was reduced from the initial pre-treatment score of 4-5 to 2 or less (5 were reduced to 0, 3 to 1 and 4 to 2). In only 1 case was the score 3. Remission of symptoms lasted for a period ranging from 11 to 108 months with an average of 51.6 months. No complications arose from the use of brachytherapy. Only one patient required embolization 3 years after the endonasal brachytherapy treatment.

The authors evaluate 32 patients affected by paranasal sinuses and nasal cavity carcinoma observed at Orl-Rt Department of Oncologic Center at Umberto l(zero) Hospital in Mestre (VE), Italy from 1985 to 1994. Among these: 16 maxillary sinus, 10 ethmoid and 6 nasal cavity carcinomas. Histologic diagnosis showed squamous cell carcinoma in 15 cases, adenocarcinoma in 8 cases, lymphoma in 2 cases, transitional cell carcinoma in 2 cases, undifferentiated carcinoma in 2 cases and adenoidocistic carcinoma in 3 cases. The mean age was 64.5 years (range 46-88 years), and mean performance status was 80 (range 60-90). Four patients had lymphonodal involvement. Eleven patients were operated, eight of them radically. All patients were treated with radiation therapy. Treatment planning was performed using Theraplan V05-B program, on extensive number of CT scans. The minimal tumor dose was 50 Gy for patients operated radically and was 60 Gy with maximum of 73-80 Gy for the others. The follow-up is 39.7 months (range 10-108). Three patients treated with radical surgery developed local relapses, two of them died. Fourteen patients treated with non radical or diagnostic surgery and radiotherapy obtained local complete remission, five of them developed local relapses inside treatment volume. Ten patients died (eight for neoplastic disease). The 3 years, 5-years and 7-years overall survival are respectively 72% and 51%. The 5-years and 7-years disease free survival rate are respectively 48% and 19% with median at 3.7 years. Complication have been minimal. Only one patient affected by glaucoma had a severe and permanent reduction of the virus. The authors conclude that 2D and 3D treatment planning can assure a better accuracy for target definition and a better precision of the treatment with a reduction of complications.

From 1985 through 1993, 113 patients affected with T1N0 glottic cancer were treated with irradiation alone at the Radiotherapy Department of Umberto I Hospital in Mestre, Italy. An anterior oblique beam of 12 MV X-rays (LINAC) or gamma-rays of a Cobalt unit were used. Dose distribution was always studied on CT scans and with a Theraplan V05-B, Theratronics. Patients age ranged 40-92 years (mean: 64.7 years) and they were mostly males. The dose was always 60 Gy/30 fractions referred to the 90% isodose. The dose to the target volume ranged 90-105%, with a mean of 99%. The follow-up ranged 26 to 98 months; the median and the mean are 38 and 40 months, respectively. Six patients had local relapses and were all operated on: cordectomy was performed in 3 of them and laryngectomy in the other 3. Radiation therapy yielded 94.7% disease control; the lesion was ultimately controlled in 100% of patients after surgical salvage. Fifteen patients died, all of them of non-neoplastic disease. The authors compared this technique with those most frequently used, i.e., wedged opposed lateral fields and wedged anterior oblique beams, and observed that it allows minimal volumes to be irradiated with maximal doses and yields results. Wedged beams are not necessary with this technique. The authors consider irradiation the treatment of choice for early glottic cancer and believe that surgery, with the conservative approach if feasible, should be limited to relapses.

The coplanar polycentric multiple 180 degrees single arc and narrow beams technique (PMA) allows high radiation doses to be delivered to the target, with similar dose distribution to that of brachytherapy. Since 1990, more than 100 patients have been treated: 80 had NSCLC, 12 had epidermoid head and neck (oral cavity and oropharynx) cancers, 8 brain tumors, 4 esophageal cancers and, sporadically, other patients had many other kinds of tumors, e.g., Hodgkin's and non-Hodgkin's lymphomas and sarcomas. X photons of a 12-MV Linac have always been used. NSCLC patients are assessable for local control, toxicity and survival, while the other patients only for local control and/or toxicity. As for 31 stage I-II lung cancer patients, CR has been observed in 82.8% of them and PR in 13.8%; the response was always assessed with chest radiography, CT, FBS, cytology and/or histology. The overall actuarial survival rate is 71% at 40 months, the disease-free survival rate is 75% and the local progression-free survival rate is 94%. As for 49 stage-III patients, CR has been observed in 40% of them and PR in 56%. The overall disease-free survival is 10% at 28 months (median survival: 14.37 +/- 0.6 months). The disease-free survival rate is 23%. The local progression-free survival rate is similar to the overall survival rate, which seems to prove the very high metastatic spread of this disease in advanced stages. Twelve head and neck cancer patients have been treated, 5 of them in stage II and 7 in stage IV. CR has been observed in all the patients in lower stages (100%), in 4/7 patients in stage IV (57%) and in 4/5 patients (80%) in the T4N0 subgroup. The response of brain tumors treated with the PMA technique is difficult to assess because radiographic, CT and MR images are difficult to correlate with patients clinical status. The patients in our series are still alive, with a medium follow-up of 7 months (range: 2-16 months). A longer follow-up is necessary before any other considerations on the effectiveness of this method can be made. This technique was used on the patients who were not eligible for the other techniques with high doses delivered to the tumor, because of its volume and/or shape. Four esophageal cancers were treated with palliative intent, because of absolute dysphagia, in alternative to HDR brachytherapy. All these patients have obtained symptom remission.(ABSTRACT TRUNCATED AT 400 WORDS)

Rendu-Osler disease is a clinical form characterized by skin, mucous and bowel teleangiectasias causing repeated bleeding, especially in the nasal region. Repeated epistaxis is controlled, however transiently, with electrocoagulation, laser therapy, embolization, mucous transplants and external radiotherapy or, more frequently, brachytherapy. The authors report on a Curietherapy technique based on the use of 192Iridium wires. The wires, which cannot be placed in parallel lines, must be positioned in three places after a fan-wise pattern: the first one on the floor, the second one along the anterior wall and the third one in between. The three wires are inserted into plastic tubes during fluoroscopy. The length of the wires is differentiated for greater dose distribution homogeneity. The dose given to the reference isodose--which is probably in contact with the mucosa--is 30 Gy. We performed 9 maneuvers in 6 patients and three of them were also treated in the contralateral nostril. Complete remission was seen in 4 patients. In 2 patients the response has lasted 18 and 32 months and 2 others have a shorter follow-up. In 5 patients we obtained a good response (mean: 58 months). Our results are in agreement with those in brachytherapy literature. Few trials are reported of external irradiation but in our personal experience, its results are poor. Brachytherapy effect is limited in time but yields major clinical benefits to the patient. Brachytherapy cannot replace other treatment methods and must therefore be considered as a palliative treatment which can improve patient's quality of life in time.

Even though brachytherapy has been used for many years to treat choroidal tumors, it is not a widespread technique because it requires much organization and operators skills. The most common methods use 60Cobalt and 106Rutenium plaques, or custom-made plaques with 125Iodine loaded seeds. Another, less common, technique uses 192Iridium wires loaded on custom-made plaques. The technique we used to treat 4 retinoblastomas and 2 choroidal melanomas uses 192Iridium wires loaded on custom-made plaques. The applicator is made of a quick drying paste poured over a sphere the same size as the eye-ball: plastic tubes are inserted, according to preliminary dosimetric measurements, to house the Iridium wires. The applicator is positioned on the eye-ball corresponding to tumor site by surgery. The Iridium sources are inserted into the plastic tubes at the end of surgical placement: this afterloading technique guarantees maximal staff protection. 192Iridium (320 keV gamma emitter) allows the dose to be transmitted deeper than with 125Iodine (30 keV gamma-emitter) and 106Rutenium (3540 keV beta-emitter). Therefore, with Iridium, the dose delivered is lower on the eye-ball surface for the same tumor dose. On the other hand, the use of 60Cobalt (1250 keV gamma-emitter) gives the healthy surrounding tissues higher doses. To conclude, this method allows us to customize the application to every single case, to reach posterior sites, to ensure radioactive protection to staff thanks to afterloading and to obtain a good depth to surface dose ratio.

From January 1984 to December 1992, twenty-eight patients affected with breast carcinoma in situ were treated with surgery (8 with radical mastectomy, 20 with quadrantectomy) at Umberto I Hospital in Mestre, Italy. The patients with multicentric lesions and treated with quadrantectomy received also radiation therapy. The dose was 50 Gy/25 fractions with 60Co and a boost of 10 Gy to the tumor bed. The mean age of our patients was 55 years (range: 34-74 years). Histology diagnosed lobular carcinoma in situ in 7 cases, intraductal carcinoma in 19 cases and comedocarcinoma in 2 cases. The median and the mean follow-up are 37 and 42 months (range: 24-128), respectively. The eight-year local control and the cause-specific survival rates are 100%. No local relapses have been observed. One patient died, of another neoplastic disease, free from breast disease. We believe that the conservative approach in breast carcinoma in situ, according to literature results and to our personal experience, should be more frequently preferred to radical surgery even in the patients with multicentric lesions.

The palliative treatment of lung atelectasis can significantly improve the quality of life in the patients who are unsuitable for cure. The authors present a new transcutaneous radiotherapy technique for treating this complication of lung cancer. After conventional and CT localization, a treatment is scheduled featuring a small (3-5 cm wide and 4-6 cm long) single 180 degrees arc beam giving 14 Gy to the 90% isodose line in two daily fractions. The treatment is repeated 3 weeks later (dosage: 28 Gy). The mean dosage to the ICRU reference point was 34 Gy; the min., max. and mean dosages to the planning target volume were 31, and 35 Gy, respectively, in 4 fractions over a 3-week period. Lesions were localized best by positioning the distal end of a fiberoscope close to the tumor and by checking its position under fluoroscopic guidance, on two orthogonal projections, immediately after every treatment session. Nine patients with histologically-proven non-small cell lung cancer were treated. They relapsed after surgery and/or full-course radiotherapy. Lung reventilation, demonstrated with fiberbronchoscopy and on chest films, was observed in 8/9 patients, in 1 of them lasting for about 40 days. In the extant 7/8 cases, it lasted longer (range: 60-180 days). Of the latter patients, 5 are alive and 2 died 60 and 86 days after treatment, with no atelectasis. The treatment was very well tolerated and severe symptoms were relieved with no complications.

From January 1984 through December 1990, 311 patients affected with breast cancer were treated with quadrantectomy plus lymphadenectomy and radiation therapy (QUART) at the Umberto I Hospital in Mestre, Italy. The patients with positive nodes (N+) were treated with adjuvant chemotherapy (CMF) or hormonotherapy (Tamoxifen) according to pausal status. Most patients were in the 5th, 6th and 7th decades of life; 60.5% of them were over 50. Staging was always performed according to TNM classification (UICC criteria) and demonstrated mostly stage-I lesions (66.9%). Overall and disease-free (NED) survival rates were 95%; mean survival rates were 7.47 (+/- 0.138) and 7.22 (+/- 0.164) years, respectively. Ten patients died (5 from breast cancer); 6 local relapses were observed and 8 metastases. Metastases were seen mostly in patients with breast cancer in the internal quadrants (QI) N0, with no statistically significant differences relative to the other groups. This is probably due to the existence of an axillary pN0 and parasternal N+ group of patients, who receive insufficient treatment.

Complex mechanisms of various nature, not only physical, can influence the patterns of metastases. We compared the patients with recurrences to the brain as the only metastatic site from breast cancer with the patients relapsing in the brain and other organs. All cases were staged and treated following professional protocols. When brain metastases were diagnosed, the patients were accurately restaged before being submitted to radiation therapy; the whole brain was irradiated with various total doses and the same fractionation. The patients underwent clinical examination before and after irradiation. Survival analysis was carried out using the product-limit method considering the following periods: total survival, relapse-free survival, elapsed time till the appearance of brain metastases, and survival after radiation therapy. The cases were grouped and compared using Mantel-Cox and Breslow methods according to the following prognostic factors: brain as the first site of recurrence, pausal state, total radiation dose, stage (TNM), T and N. No significant difference in survival was observed between the cases with brain as the first metastasized organ and the others. The patients were grouped according to the extant prognostic factors: longer total and postirradiation survival rates were observed in patients in premenopausal state (Breslow: p = 0.025 and 0.005) and in the cases treated with total radiation doses greater than 40 Gy (Breslow: p = 0.023 and 0.005). T levels seemed to significantly affect all the examined periods--which influences the stage effect. Conversely, N levels seemed to be of no significant value. The menopausal factor may reflect the effects of age, from which it cannot be separated. These results can be useful for treatment planning.

Radiation therapy seems to induce depletion of lymphocytes, which are very important cells for immunity response. The lymphocyte phenotype was studied in 41 non-pretreated patients with normal immunological parameters who received postoperative radiation therapy for breast, mediastinal or pelvic cancer with at least 50 Gy/25 fractions. The functional immunological assessment was analyzed by Multiskin test (Merieux) too. The lymphocyte phenotype was determined on whole-blood lysate employing an Ortho double-fluorescence cytofluorimeter. All patients, after radiation treatment, exhibited decrement in absolute and percent lymphocyte subpopulations; the Multiskin test demonstrated simultaneous change in skin-test response. The results are highly significant (p 2-tailed area less than 0.0001) for absolute cells count and skin-delayed response test, but percent variations are not significant when verified by t-test.

The radiation therapy of internal mammary chain, according to many other authors, is indicated in patients with N + breast cancer or with inner quadrant disease. Since the direct field with gamma radiation seems to induce important adverse effects on myocardium, the authors were induced to check experimentally dose distributions of 12-15 MeV electron beams and compare the results to gamma photon dose distribution. Materials and dosimetric methods as well as experimental results are described. Moreover theoretic and practical point of view are discussed coming to the conclusion that electron beams are more suitable for myocardial saving. Nevertheless some technical variations are required, to maintain the typical homogeneity of photon beams.

The results are reported of a multidisciplinary diagnostic and therapeutic program applied to 381 patients with lung carcinoma from 1983 through 1985 at Mestre General Hospital. Cytologic and/or histologic diagnosis was established in 95% and staging accomplished in 96% of the patients. One-hundred-twenty-nine patients with non-small cell cancer were primarily treated by surgery (lobectomy or pneumonectomy); 3-year survival of this group was 48%. Of the 45 patients with pN1 or pN2 disease, 23 were treated with postoperative adjunctive mediastinal radiotherapy (50Gy/25 F/5Wk); however, survival showed no significant difference in the two groups. Ninety-seven inoperable patients were treated by radiotherapy alone; among those receiving doses of 50-60 Gy in 5 to 6 weeks, 3-year survival was 10%. Chemotherapy (CAMP), used in 23 cases (22 stage IV, 1 stage III), showed no improvement in survival, as compared with a similar series of patients submitted to symptomatic treatment alone. Of the 27 patients affected by small-cell carcinoma, 14 were treated with an aggressive radiochemotherapy protocol and 13 with palliative radiotherapy or low-dose chemotherapy: median survival in the two groups was respectively 45 and 60 weeks. Our study demonstrates the clinical feasibility of interdisciplinary programs routinely applied to a large population of lung cancer patients, and confirms its rationale in terms of early diagnosis, improved staging, and adequate treatment.

The three-field technique is the most common method used for breast and regional node treatment after conservative surgery. Several variants of this technique, which are characterized by complex geometrical problems, have been described. A possible simplification of this technique and the use of individualized shielding blocks both for anterior and for tangential fields is proposed, thus allowing for the simultaneous shielding of the half beam and the critical areas. Advantages of isocentrical techniques are thereby maintained, but the number of mechanical movements required is minimized and collimators and couch rotations are not needed. Patient set-up time is also greatly shortened. The accuracy of this technique has been verified using both photographic methods and thermoluminescent dosimetry.

Between January 1981 and December 1985, 364 female patients underwent surgical treatment for breast cancer in Mestre General Hospital. The pathological stage of the disease was stage I in 60 patients, stage II in 215 patients, stage III A in 30 patients, stage III B in 44 patients and stage IV in 15 patients. The patients with T1-T2 N0 lesions located in the outer quadrants received no additional treatment after surgery, while the others received adjuvant therapy. The patients with stage-IV disease (M+) were treated with chemo and/or hormonotherapy. All patients were followed for an average of 33 months up to December 1986 (range 1-71 months). Local-regional relapses developed in 17 patients, 15 on the chest wall and 2 in the drainage lymph nodes (only 7 within the previously-treated area). A 5-year actuarial survival rate was observed of about 78%, and 66% of relapse-free survival, in the whole group of patients (100% and 92% in stage I; 92.5% and 76% in stage II; 51% and 33% in stage III A; 32% and 19% in stage III B; 31% in stage IV, respectively). As far as our series of patients is concerned, the massive involvement of axillary lymph nodes seems to be the most adverse prognostic factor in survival rates. Even though the short follow-up does not allow definitive conclusions to be drawn, the authors believe such loco-regional treatments as surgery and radiation therapy to be extremely important in the local control of breast cancers, as well as in the patients' survival in the long run.