Consolidative active scanning proton therapy for mediastinal lymphoma: selection criteria, treatment implementation and clinical feasibility.

AIMS: Proton therapy (PT) represents an advanced form of radiotherapy with unique physical properties which could be of great advantage in reducing long-term radiation morbidity for cancer survivors. Here, we aim to describe the whole process leading to the clinical implementation of consolidative active scanning proton therapy treatment (PT) for mediastinal lymphoma. METHODS: The process included administrative, technical and clinical issues. Authorization of PT is required in all cases as mediastinal lymphoma is currently not on the list of diseases reimbursable by the Italian National Health Service. Technically, active scanning PT treatment for mediastinal lymphoma is complex, due to the interaction between actively scanned protons and the usually irregular and large volumes to be irradiated, the nearby healthy tissues and the target motion caused by breathing. A road map to implement the technical procedures was prepared. The clinical selection of patients was of utmost importance and took into account both patient and tumor characteristics. RESULTS: The first mediastinal lymphoma was treated at our PT center in 2018, four years after the start of the clinical activities. The treatment technique implementation included mechanical deep inspiration breath-hold simulation computed tomography (CT), clinical target volume (CTV)-based multifield optimization planning and plan robustness analysis. The ultimate authorization rate was 93%. In 4 cases a proton-photon plan comparison was required. Between May 2018 and February, 2021, 14 patients were treated with consolidative PT. The main clinical reasons for choosing PT over photons was a bulky disease in 8 patients (57%), patient's age in 11 patients (78%) and the proximity of the lymphoma to cardiac structures in 10 patients (71%). With a median follow-up of 15 months (range, 1-33 months) all patients but one (out-of-field relapse) are without evidence of disease, all are alive and no late toxicities were observed during the follow-up period. CONCLUSIONS: The clinical implementation of consolidative active scanning PT for mediastinal lymphoma required specific technical procedures and a prolonged experience with PT treatments. An accurate selection of patients for which PT could be of advantage in comparison with photons is mandatory.

Clinical results of proton therapy reirradiation for recurrent nasopharyngeal carcinoma.

Background and purpose: Recurrent nasopharyngeal carcinoma (NPC) has limited curative treatment options. Reirradiation is the only potential definitive treatment in advanced stages at a cost of substantial severe and often life-threatening toxicity. Proton therapy (PT) reduces irradiated volume compared with X-ray radiotherapy and could be advantageous in terms of safety and efficacy in a population of heavily pretreated patients. We report the retrospective results of PT reirradiation in recurrent NPC patients treated at our Institution Methods: All recurrent NPC patients treated since the beginning of clinical activity entered the present analysis. Clinical target volume consisted of Gross Tumor volume plus a patient-specific margin depending on disease behavior, tumor location, proximity of organs at risk, previous radiation dose. No elective nodal irradiation was performed. Active scanning technique with the use of Single Field Optimization (SFO) or Multifield Optimization (MFO) was adopted. Cumulative X-ray -PT doses were calculated for all patients using a dose accumulation tool since 2016. Treatment toxicity was retrospectively collected. Results: Between February 2015, and October 2018, 17 recurrent NPC patients were treated. Median follow-up (FUP) was 10 months (range 2-41). Median PT reirradiation dose was 60 Gy RBE (range 30.6-66). The majority of patients (53%) underwent concomitant chemotherapy. Acute toxicity was low with no ≥ G3 adverse events. Late events ≥ G3 occurred in 23.5% of patients. Most frequent late toxicity was hearing impairment (17,6%). G2 soft tissue necrosis occurred in two patients. Fatal bleeding of uncertain cause (either tumor recurrence or G5 carotid blowout) occurred in one patient. Kaplan-Meier 18 months Overall Survival (OS) and Local control (LC) rates were 54.4% and 66.6%, respectively. Conclusions: Our initial results with the use of modern PT for reirradiation of recurrent NPC patients are encouraging. Favorable LC and OS rates were obtained at the cost of acceptable severe late toxicity.

Adjuvant intensity-modulated proton therapy in malignant pleural mesothelioma. A comparison with intensity-modulated radiotherapy and a spot size variation assessment.

PURPOSE: Intensity-modulated radiation therapy (IMRT) is the state-of-the-art treatment for patients with malignant pleural mesothelioma (MPM). The goal of this work was to assess whether intensity-modulated proton therapy (IMPT) could further improve the dosimetric results allowed by IMRT. PATIENTS AND METHODS: We re-planned 7 MPM cases using both photons and protons, by carrying out IMRT and IMPT plans. For both techniques, conventional dose comparisons and normal tissue complication probability (NTCP) analysis were performed. In 3 cases, additional IMPT plans were generated with different beam dimensions. RESULTS: IMPT allowed a slight improvement in target coverage and clear advantages in dose conformity (p < 0.001) and dose homogeneity (p = 0.01). Better organ at risk (OAR) sparing was obtained with IMPT, in particular for the liver (D(mean) reduction of 9.5 Gy, p = 0.001) and ipsilateral kidney (V(20) reduction of 58%, p = 0.001), together with a very large reduction of mean dose for the contralateral lung (0.2 Gy vs 6.1 Gy, p = 0.0001). NTCP values for the liver showed a systematic superiority of IMPT with respect to IMRT for both the esophagus (average NTCP 14% vs. 30.5%) and the ipsilateral kidney (p = 0.001). Concerning plans obtained with different spot dimensions, a slight loss of target coverage was observed along with sigma increase, while maintaining OAR irradiation always under planning constraints. CONCLUSION: Results suggest that IMPT allows better OAR sparing with respect to IMRT, mainly for the liver, ipsilateral kidney, and contralateral lung. The use of a spot dimension larger than 3 × 3 mm (up to 9 × 9 mm) does not compromise dosimetric results and allows a shorter delivery time.

[Exclusive intra-operative radiation therapy (IORT) for early stage breast cancer: pilot study of feasibility]. / Radioterapia intraoperatoria (IORT) esclusiva nel carcinoma iniziale della mammella: studio pilota di fattibilità.

AIM: To evaluate feasibility, tolerability and cosmetic outcome of intra-operative radiation therapy (IORT) as an exclusive post-surgery treatment of early stage breast cancer. PATIENTS AND METHODS: From October 2008 to October 2009 30 patients underwent wide breast cancer excision or quadrantectomy followed by IORT on tumor bed with accelerated electrons at the dose of 21Gy. The characteristics of the patients were: ductal breast cancer or invasive lobular cT1, cT2 ≤ 2,5 cm, cN0, G1-2, age over 35 years, M0. RESULTS: The average age was 51.7 (range 38 - 75) with an average follow up of 11.7 months (range 6 - 18). The pathologic stage of the lesions resulted pT1 in 29 cases (96,6%), in particular: one case pT1a (3,3%), 21 cases pT1b (70,0%) and 7 cases pT1c (23,3%). One case (3,3%) was pT2 with a diameter of 2.5 cm. The grading was G2 in 20 cases (66,6%) and G1 in 10 cases (33,3%). The toxicity, evaluated according to the EORTC-RTOG criteria, was G0 (33.3%) in 10 cases, G1 (63,3%) in 19 cases, G2 in one case (3,4%); there was no G3 toxicity. The time needed for a complete healing of the wound was less than 10 days in 96,7% of the cases, with one case of limphocele (3,3%). There were no infections of the surgical wound nor any mastitis, neither in the treated quadrant nor in the other ones. We observed a light fibrosis in 5 cases (16,6%), moderate in 2 cases (6,6%) but never severe. Cosmetics, evaluated in four levels, according to Danoff et al., was excellent in 3 cases (43,3%), good in 15 cases (50%), sufficient in 2 cases (6,7%), never insufficient. As regards local control, there was no local relapse. The global survival was 100%. CONCLUSIONS: The IORT in early breast cancer, at the doses used in this study, proved itself as a secure technique, repeatable, with limited complications. The advantages of its use are the possibility of a direct control, by the surgeon and the radiotherapist, of the structures to treat and those to protect; the absence of time needed for cellular repopulation between surgery and radiotherapy; a good cosmetic outcome; and logistic advantages. It is necessary to have a long term follow up to evaluate the efficacy in terms of long term cosmetic and local control.

The role of fractionated radiotherapy and radiosurgery in the management of patients with craniopharyngioma.

The optimal management of craniopharyngiomas remains controversial. The first-line treatment usually consists of surgical resection. Complete tumor removal provides a high rate of long-term control; however, aggressive surgery is associated with significant incidence of complications. Radiotherapy (RT) is currently used in patients after limited surgery and achieves excellent long-term tumor control. Stereotactic radiotherapy, both in the form of radiosurgery (RS) or fractionated stereotactic radiotherapy (FSRT), has been developed as a more accurate technique of irradiation with more precise tumor localization and consequently a reduction in the volume of normal brain irradiated to high radiation doses. We provide a review of published data on outcome of conventional fractionated RT and modern radiation techniques. FSRT is a suitable treatment technique for all sizes of craniopharyngiomas, and efficacy is comparable to conventional RT. Single-fraction stereotactic radiosurgery is usually delivered to small tumors away from critical structures. Longer follow-up is necessary to confirm the excellent tumor control and the potential reduction of long-term radiation toxicity.

Effects of fluconazole in the prophylaxis of oropharyngeal candidiasis in patients undergoing radiotherapy for head and neck tumour: results from a double-blind placebo-controlled trial.

Fluconazole is recommended in the prophylaxis of oropharyngeal candidiasis (OPC) in patients undergoing radiotherapy for head-neck tumours; however, the actual effectiveness of fluconazole in this setting remains unclear. Adult patients with cervico-cephalic carcinoma submitted to radical or adjuvant radiotherapy were randomized to 100 mg fluconazole (n = 138) or matched placebo (n = 132) oral suspension once daily from the sixth session of radiotherapy up to the end of treatment. The final analysis of the investigation showed a higher rate of the OPC outbreak-free survival in the fluconazole compared with placebo (P = 0.008 in the log-rank test). The mean time (95% CI) to OPC outbreak was 56 (53-59) days in the fluconazole group and 47 (43-51) days with placebo. The mean duration of radiotherapy was 43.5 and 39.9 days, respectively in the two groups (P = 0.027). Adverse effects were reported in 70.3% of patients in the fluconazole group and in 67.4% with placebo. The results showed prophylaxis with fluconazole given in irradiated patients with head-neck tumours significantly reduces the rate and the time to development of OPC compared with placebo.

Phase II study of preoperative irradiation and chemotherapy with capecitabine in patients with locally advanced rectal carcinoma.

Preoperative chemoradiotherapy has demonstrated to improve resectability and local control in locally advanced rectal cancer (LARC). 5-fluorouracil (5FU) has traditionally been the drug of choice in combination with radiation therapy. Early studies of capecitabine (CAP) have shown its potential to replace 5FU. Between March 2002 and April 2005, 31 patients with newly diagnosed LARC (T2 N+ 2 cases, T3 N0-N+ 25 cases, T4 N0-N+ 4 cases) received the combined treatment. Surgery was planned 6-8 weeks after chemoradiation. Adjuvant chemotherapy with 5FU plus leucovorin for 6 courses was given in pN+ patients. All patients completed the planned treatment. Grade 3 acute toxicity was observed in 5 patients (16%). Nineteen patients (61%) had a downstaging. A complete pathological remission was observed in 3 cases (10%). Median follow-up is of 23 months (range; 6-36 months). The results of this experience confirm the data of the literature about the feasibility and efficacy of a neoadjuvant treatment with radiation and CAP in LARC.

Axillary irradiation omitting axillary dissection in breast cancer: is there a role for shoulder-sparing proton therapy?

The recent EORTC 10981-22023 AMAROS trial showed that axillary radiotherapy and axillary lymph node dissection provide comparable local control and reduced lymphoedema in the irradiated group. However, no significant differences between the two groups in range of motion and quality of life were reported. It has been acknowledged that axillary irradiation could have induced some toxicity, particularly shoulder function impairment. In fact, conventional breast irradiation by tangential beams has to be modified to achieve full-dose coverage of the axillary nodes, including in the treatment field a larger portion of the shoulder structures. In this scenario, alternative irradiation techniques were discussed. Compared with modern photon techniques, axillary irradiation by proton therapy has the potential for sparing the shoulder without detrimental increase of the medium-to-low doses to the other normal tissues.

Ten-year results of treatment of ductal carcinoma in situ (DCIS) of the breast with conservative surgery and radiotherapy.

The optimal treatment of ductal carcinoma in situ (DCIS) of the breast has not yet been established. The effectiveness of adjuvant postoperative radiotherapy after conservative surgery is debated. Few data are available in Italy on the combined treatment. A collaborative multi-institutional study on this issue in 10 radiation oncology departments of the north-east of Italy was conducted. One hundred and thirty nine women with DCIS of the breast were treated between 1980 and 1990. Age ranged between 28 and 88 years (median 50 years). Surgical procedures were: quadrantectomy in 108, lumpectomy in 22 and wide excision in 9 cases. The axilla was surgically staged in 97 cases: all the patients were node-negative. Radiation therapy was delivered with 60Co units (78%) or 6 MV linear accelerators (22%) for a median total dose to the entire breast of 50 Gy (mean 49.48 Gy; range 45-60 Gy). The tumour bed was boosted in 109 cases (78%) at a dose of 4-30 Gy (median 10 Gy) for a minimum tumour dose of 58 Gy. Median follow-up was 81 months. Thirteen local recurrences were recorded, 7 intraductal and 6 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease. Actuarial overall, cause-specific and recurrence-free survival at 10 years are of 93%, 100% and 86%, respectively. The results of this retrospective multicentric study substantiate the favourable data reported in the literature and confirm the efficacy of the breast-conserving treatment of DCIS employing conservative surgery and adjuvant radiation therapy.

Report of long-term follow-up in a randomized trial comparing radiation therapy and radiation therapy plus hyperthermia to metastatic lymph nodes in stage IV head and neck patients.

PURPOSE: The treatment of inoperable metastatic lymph nodes in patients with head and neck cancer represents a therapeutic challenge. Clinical results using conventional radiation therapy are disappointing; on the other hand, the evaluation of recent innovative radiotherapeutic methods is still pending. The end points of this analysis were focused on long-term local control, on its potential influence on survival, and on late toxicity of a previously reported randomized Phase III study comparing conventionally fractionated radical irradiation alone or combined with local hyperthermia in fixed and inoperable metastatic neck lymph nodes. METHODS AND MATERIALS: The medical records of 41 patients (44 nodes) with advanced locoregional Stage IV squamous cell cancer of the head and neck and randomized to treatment in the period 1985-1986 with irradiation alone (22/23 evaluable nodes) or combined with external hyperthermia (18/21 evaluable nodes), were re-evaluated. RESULTS: The statistically significant difference observed in "early" response (p = 0.0164) in favor of the combined treatment results in improved 5-year actuarial nodal control (p = 0.015). Clinical improvement noted in tumor control positively affects survival, leading to a statistically significant difference in survival at 5 years (p = 0.02). With respect to side effects, no clearly enhanced acute or late toxicity has been found; as severe late effects, two patients with bone necroses possibly related to the combined treatment have been observed. Thermal analysis failed to show a significant correlation between heating parameters and the end points of the study. CONCLUSION: This report with 5-year follow-up confirms the efficacy and the absence of severe toxicity of the combination of radical radiation and hyperthermia in the treatment of metastatic lymph nodes in Stage IV squamous cell carcinoma of the head and neck.

Radical radiation alone versus radical radiation plus microwave hyperthermia for N3 (TNM-UICC) neck nodes: a prospective randomized clinical trial.

Between September 1985 and December 1986, 44 N3 (TNM-UICC) metastatic squamous cell cervical lymph-nodes were randomized to receive conventionally fractionated radical irradiation (RT) to a total dose of 64-70 Gy, or conventionally fractionated radical irradiation plus twice a week local microwave hyperthermia (Ht). The two major end points of this study were (a) local control rates evaluated at 3 months after the end of combined therapy and (b) incidence of acute local toxicity. Thirty-six nodes (82%) were evaluable as of December 1986, at which time there was a premature closure of this study due to ethical reasons. An interim analysis had revealed a statistically significant difference in complete response rates in favor of the combined arm (p = 0.0152). The complete response rates were 82.3% (14/17) for the combined treatment arm versus 36.8% (7/19) for the control irradiation arm, leading to an iso-dose thermal enhancement ratio (TER) value of 2.23. Both arms are comparable in average total RT dose delivered (RT: 67.05 Gy; RT + Ht: 67.85 Gy) and in average maximum node diameter (RT arm: 4.81 cm; RT + Ht: 4.88 cm). Acute local toxicities were similar in irradiated and heated plus irradiated neck regions; only one skin burn was observed. As possible treatment related death, one patient in the RT + Ht arm died 2 months after completion of therapy with a carotid rupture associated with extensive tumor necrosis. These results confirm previous non-randomized reports suggesting that hyperthermia in combination with full dose conventionally fractionated irradiation significantly enhances the chance of early local control of fixed N3 neck nodes without exhibiting an increase of acute local toxicity.

Cisplatin, hyperthermia, and radiation (trimodal therapy) in patients with locally advanced head and neck tumors: a phase I-II study.

PURPOSE: Hyperthermia is now being widely used to treat clinical malignancies especially combined with radiotherapy and more rarely with chemotherapy. The combination of heat, radiation, and chemotherapy (trimodality) can lead to potent interaction. The present Phase I-II study was conducted to evaluate the feasibility and acute toxicity of a combination of cisplatin, hyperthermia, and irradiation in the treatment of superficial cervical nodal metastases from head and neck cancer. METHODS AND MATERIALS: Eighteen patients with measurable neck metastases from previously untreated squamous cell head and neck tumors were entered into the trial. Therapy consisted of a conventional irradiation (total dose 70 Gy, 2 Gy five times a week) combined with a weekly administration of 20 mg/m2 iv of cisplatin and a total of two sessions of local external microwave hyperthermia (desired temperature of 42.5 degrees C for 30 min). RESULTS: Feasibility of the treatment was demonstrated. Acute local toxicity was mild; no thermal blisters or ulcerations were reported and only two patients experienced local pain during hyperthermia. Cutaneous toxicity appeared greater than in our previous studies with irradiation plus hyperthermia and irradiation plus cisplatin. Systemic toxicity was moderate with major toxic effects observed in three patients (World Health Organization (WHO) grade 3 anaemia). Even though it was not an aim of the study to evaluate the nodal response, we observed a complete response rate of 72.2% (95% confidence interval 51-93.4%), 16.6% of partial response and 11.1% of no change. CONCLUSION: The study confirms the feasibility of the combination of cisplatin, heat, and radiation with an acceptable toxicity profile. The trimodal therapy deserves further evaluation as a way to enhance the efficacy of irradiation in the treatment of nodal metastases from head and neck tumors.

Patterns of radiotherapy for early breast cancer in Northern Italy compared with European and national standards.

PURPOSE: To assess the current practice of early breast cancer (EBC) post-operative irradiation in Northern Italy and to evaluate its conformance with European standards and recently defined national guidelines. MATERIALS AND METHODS: Fifty Radiotherapy departments in Northern Italy received a questionnaire assessing parameters on pre-treatment evaluation of patients, on preparation, prescription and execution phases of irradiation (XRT), on surgery-XRT-chemotherapy integration and on follow-up. The analysis of collected information was compared with both the 1991 EORTC-EUSOMA guidelines and the 1997 AIRO (Italian Association for Radiation Oncology) minimal requirements on EBC post-operative irradiation. RESULTS: Thirty-nine out of 50 (78%) departments answered the questionnaire. All treat T1-T2 tumours, after tumourectomy or, mostly, quadrantectomy. The mean interval between surgery and XRT is 45 +/- 14 days. Chemotherapy is delivered concurrently in 70% of departments, CTV is represented by residual mammary gland in 100% of cases, while 38% and 52% of departments occasionally treat internal mammary and axillary or supra-clavicular nodes, respectively. Total dose delivered to the whole breast is 46-50 Gy in 98% (1.8-2 Gy/fraction). The tumour bed is boosted in 79% of cases. An immobilization device is used in 28% of cases CTV is clinically localized in 62% of patients. Tangential fields are simulated in 85% of centres, with film storage in 78% of cases. Co-60 units are used in 58% and/or 4-6 MV X-rays in 70% of centres, mostly utilizing beam modifiers. Computerized treatment planning is performed in 95% of cases. Fifty-five percent of departments prescribe the dose at the ICRU point. Portal films are routinely taken in 50% of cases. Boost irradiation is mainly performed using external XRT. Lastly, acute and late side effects and cosmesis are respectively evaluated in 100%, 98% and 90% of centres. CONCLUSIONS: Results on current practice in Northern Italy generally show a good conformance with European standards. However, some variables related to treatment prescription, simulation and treatment planning need to be standardized. This set of information was largely utilized by the AIRO to define national guidelines adapted to the Italian resources and situation.

Quality of life after radiotherapy for early-stage testicular seminoma.

BACKGROUND AND PURPOSE: Standard therapy in early-stage testicular seminoma (TS) includes inguinal orchiectomy followed by irradiation (XRT) of the pelvic and para-aortic nodes. Since this treatment is highly effective in controlling the disease and leads to many long survivors, the quality of life (QL) may be impaired by treatment-induced side-effects. The aim of this study was to provide a QL evaluation of patients treated with XRT after orchiectomy for TS. MATERIALS AND METHODS: We used a validated self-completed questionnaire based on a series of 44 items covering all QL fields. The items were grouped into six subscales with standardized scores. The questionnaire was mailed to a consecutive series of 143 patients treated between 1961 and 1995 for TS with no evidence of disease after primary treatment. RESULTS: Ninety-eight questionnaires (68.5%) were returned and are assessable. The median age of the patients was 48 years (range, 26-85 years) at the time of completing the questionnaire, with a median follow-up after completion of treatment of 123 months (range, 15-432 months). The physical and autonomy subscale standardized scores were > or =1 in 83 and 95% of the cases, respectively. Psychological problems were reported by a small percentage of patients, ranging from 13, who reported a depressive condition, to 16%, who declared feeling tense. Of the patients, 86 and 89% have regularly met relatives and friends. The urinary score was above the central point in 99% of the patients. Only 6% of the patients perceived their body image as worsened by treatment. The patients who were more informed about the disease and therapy had a better physical and psychological adjustment. CONCLUSIONS: The QL in our patients resulted as satisfactory, with a maintained body image and few side-effects. The information given to the patients about their disease and its treatment influenced the post-treatment QL adjustment.

Hyperfractionated radiation in combination with local hyperthermia in the treatment of advanced squamous cell carcinoma of the head and neck: a phase I-II study.

Twenty-seven patients with cervical metastases from squamous cell head and neck tumours were treated with hyperfractionated XRT (total dose 69.60-76.80 Gy, 1.2 Gy b.i.d. five times a week) combined with a total of two to six sessions of superficial external HT. Acute local toxicity was mild; as major acute side effects, only one ulceration was recorded. No severe late side effects were observed. Late toxicity was similar to that observed in our previous studies with the combination of heat and radiation. Nodal complete response was observed in 77% of patients, partial response was observed in 15% of patients and no change was observed in 8% of patients. Five-year actuarial nodal control was 64.5 +/- 19% and 5-year actuarial survival was 24 +/- 10%. The treatment of nodal metastases from head and neck tumours with the combination of HT and hyperfractionated XRT is feasible with an acceptable acute and late toxicity profile.

p21 expression in colorectal carcinomas: a study on 103 cases with analysis of p53 gene mutation/expression and clinic-pathological correlations.

The WAF1/CIP1 gene product, p21, an inhibitor of cyclin-dependent kinases, is a critical downstream effector in the p53 pathway. The expression of p21 in human neoplasms is heterogeneous, and may be related to p53 functional status. We evaluated p21 immunoreactivity in 103 colorectal carcinomas (CC) in relation to the p53 gene and protein alterations and clinico-pathologic parameters. High p21 expression (more than 10% reactive cells) was seen in 39% of cases. p21 staining was heterogeneous and often detected in clusters of tumour cells; in some tumours p21 staining was more pronounced in superficial areas. No relation was seen between p21 immunoreactivity and site of the tumours (right vs left), TNM stage and grade. p21 expression was related to p53 status as evaluated with IHC or with SSCP analyses, low p21 expression usually being associated with p53 protein overexpression (P=0.048) and p53 gene alteration (P=0.005). The strongest associations were seen when the combined p53/p21 immunophenotype was compared with p53 gene alterations (P=0.0002). These data support the hypothesis that p21 expression in CC is mainly related to p53 functional status, suggesting that p21 expression could be an interesting adjunct in the evaluation of the functional status of the p53 pathway in CC.

Ocular metastases from breast carcinoma: A multicentric retrospective study.

Breast cancer may affect the eye and orbit by metastatic neoplastic infiltration, uvea being the most common site of presentation. Management of these cases with radiotherapy is usually gratifying with reported response rate of approximately 75%. A retrospective evaluation of cases treated in five Institutions participating in a collaborative radiation therapy group of north-Italy is reported. Fifty-four cases of metastases to the eye or orbit were referred for radiation therapy to the Departments participating in the survey in the period 1977-1995. There were 49 female patients aged between 28 and 75 years (median, 44 years) at presentation of orbital metastasis. Thirty-eight lesions (70%) were metastases to the choroid, 9 involved other parts of the eye, and 7 patients had orbital metastases. Five of the 49 patients had bilateral choroidal metastases. Radiotherapy was employed with megavoltage equipment. The median total dose delivered was 40 Gy (range, 16-60 Gy). All the patients were treated 5 times per week with fraction sizes ranging from 1.8 to 3.0 Gy (median, 2.0 Gy). Of the 43 evaluable eyes, 34 (79%) showed a definite improvement after radiotherapy. There was a stabilization of the process in 4 patients. The rest (11 lesions) were lost to detailed follow-up of the response of the eye metastases. Twelve patients experienced acute transient cheratoconjunctivitis and in a case a subconjunctival haemorrhage was observed; as late side effects, two cases of chataract were observed during a period of observation of 37 and 117 months. A median survival time of 17 months was observed. The goal of irradiation was to improve vision or at least prevent blindness and enucleation. The palliative effect of irradiation was confirmed with a response rate consistent with the data of the literature on this subject.

Primary non-Hodgkin's lymphoma of the female genital tract.

Genital tract lymphoma is a rare disease; information on diagnosis, treatment and outcome are limited. We report on eight patients affected by non-Hodgkin's lymphoma of the genital tract, five from the cervix, two from the vagina and one from the vulva collected between 1987 and 1998. Age at presentation ranged from 36 to 82 (median 67) years. The commonest initial symptom was vaginal bleeding, post coital in 1 patient. Three patients complained of vescical symptoms. Ann Arbor classification was stage IAE for 6 patients. Histology, according to the IWF, was either intermediate grade (4 patients), or high grade (3 patients), not evaluable in one case. Seven patients were treated with chemotherapy (anthracycline based in four) followed by pelvic radiotherapy in five; one patient received irradiation alone. Five patients are currently alive and free of disease with follow-up ranging from 8 to 126 months. Based on our experience in this series, we support a management scheme of combination chemotherapy and radiotherapy for patients with non-Hodgkin's lymphoma of the genital tract.

Use of 5-fluorouracil, epirubicin and mitomycin C (FEM) as adjuvant therapy in node-positive, radically-resected gastric cancer patients: survey of a general hospital experience.

Between 1/1986 and 6/1996, 37 consecutive patients affected by node-positive gastric cancer (GC) were treated with radical surgery and received 5-fluorouracil, epirubicin and mitomycin C (FEM) as adjuvant treatment. Only 57% of the patients received all six cycles and the reasons for treatment withdrawal were mainly related to concomitant pathologies and prolonged leukopenia. After a median follow-up of 39 months, the 3-year disease-free survival, disease-related survival and overall survival were 75.8%, 83.7% and 78.6% respectively. A statistically significant difference in survival was found in the subgroup of patients receiving more than three courses of treatment.

Primary adenoid cystic carcinoma of the Bartholin's gland: a clinical, histological and immunocytochemical study of a case.

Adenoid cystic carcinoma of the Bartholin's gland is a rare tumor. Only 41 cases, to our knowledge, have been described in literature. It is impossible, at present, to determine the best management of this disease. Local recurrence and distant metastases (mainly of the lung) frequently occur. A case of adenoid cystic carcinoma of the Bartholin's gland is looked into with respect to clinical and immunohistochemical characteristics. Radiation therapy is suggested as effective together with surgery. The efficacy of routine lymphadenectomy has not been demonstrated. The case reported is the first described with nodal metastasis as single mode of recurrences presentation.