Sequential and/or concurrent hypofractionated radiotherapy and concurrent chemotherapy in neoadjuvant treatment of advanced adenocarcinoma of the pancreas. Outcome and patterns of failure

BACKGROUND/AIMS: To investigate treatment outcome and patterns of failure of sequential chemotherapy (CHT) and/or concurrent hypofractionated radiotherapy (RT) and CHT followed by surgery in locally advanced non-metastatic pancreatic adenocarcinoma. METHODOLOGY: Seven patients with locally advanced but marginal resectable tumors (close contact but no signs of infiltration of the mesenteric vessels and/or vena portae) were treated with hypofractionated RT (5x3 Gy per week) and concurrent continuous infusion (300 mg/sqm/24 h, 7 days per week) of 5-fluorouracil (FU). Ten patients with locally advanced disease with radiologically suspected infiltration of the mesenteric vessels and/or v. portae were treated with 2 cycles of Cisplatin (75 mg/sqm) and Gemcitabine (2x1250 mg/sqm), and patients without tumor progression received the same concurrent RT/CHT as group 1. Four weeks after RT/CHT radical pancreatectomy was planned for patients with stable disease or remission. RESULTS: Toxicity was low in both groups, with no CTC grade 4 toxicity. In group 1, RT/CHT was completed in all patients. There was no radiological remission, but stable disease in 5 out of 7 patients. All 5 patients underwent resection of the primary tumor with a R0-resection in 3 patients. In group 2, 8 patients completed CHT and RT/CHT treatment as planned. There were 3 with partial remission. Operation was done in 4 patients, but only one R0 resection was achieved. The median survival time for all 17 patients is 13 months, with 1- and 2-year survival being 53% and 18%, respectively. Local progression was observed in 9, peritoneal seeding in 7 and distant metastasis (mostly liver and lung) in 8 patients. CONCLUSIONS: The neoadjuvant therapy could be administered with low toxicity. Results of this study warrant further investigation aiming at optimal tailoring in of this treatment approach in these two subgroups of patients.     

Characteristics and outcome of therapy‐related myeloid neoplasms: Report from the Italian network on secondary leukemias

Therapy‐related myeloid neoplasms (t‐MN) are a complication of cytotoxic treatment for primary tumors and autoimmune diseases. We report data on 277 t‐MN patients, recruited between 1999 and 2013 by the Italian Network on Secondary Leukemias (104 retrospectively and 173 prospectively registered). Median age at t‐MN diagnosis was 64 years (range, 21–87). Most frequent primary malignancies (PMs) were lymphoproliferative diseases and breast cancer. One hundred and thirty‐three patients had received chemotherapy (CHT), 43 patients radiotherapy (RT), and 101 patients combined CHT/RT for PM. Median time between cytotoxic treatment and t‐MN was 5.7 years, with t‐MN following RT alone associated with significantly longer latency, compared to CHT or combined CHT/RT (mean, 11.2 vs. 7.1 years, P = 0.0005). The addition of topoisomerase‐II inhibitors to alkylating agents was associated with shorter latency compared to alkylating agents alone (median, 6 vs. 8.4 years, P = 0.02). Median survival was 14.6 months from t‐MN diagnosis, and was significantly longer in patients treated with allogeneic stem cell transplantation. Significant factors for survival at the multivariable analysis included age, adverse karyotype, and degree of anemia. Our data underline the prognostic importance of karyotype and age in t‐MN, similar to de novo acute myeloid leukemia. Treatment approaches should not preclude the use of conventional treatments for younger t‐MN patients, including allogeneic stem cell transplantation as potentially curative approach. Am. J. Hematol. 90:E80–E85, 2015. © 2015 Wiley Periodicals, Inc.     

A multimodality therapeutic approach in anaplastic thyroid carcinoma: study on 39 patients

The aim of this study was to investigate the role of multimodality treatment in patients with anaplastic thyroid carcinoma. From 1992 to 1999, 39 consecutive patients with a histologically or cytologically proven anaplastic thyroid carcinoma were referred to the Thyroid Center of Padua General Hospital. There were 28 females and 11 males with a median age of 69 years (range 39-88 years). About one-third of patients had a history of preceeding nodular goiter. Two patients had areas of differentiated thyroid carcinoma at histological examination. Local disease was present in 26 patients while distant metastases, mainly to the lung, were present in 22 at diagnosis or quickly developed during the observation period in all the others except one. Thirty-two patients were previously untreated: 9 of them were in good general condition, 1 had limited lung metastases, and the tumor mass was considered resectable by the surgeon. These 9 patients were treated with cisplatin once a week and radiotherapy (RT) 36Gy in 18 fractions over three weeks, followed by total thyroidectomy (TT) and by further chemotherapy (CHT) with adriamycin and bleomycin in 4 patients. Seven patients, 3 with lung metastases at diagnosis, had undergone TT, followed by RT in 5, in another hospital and were subsequently referred to our center due to the presence of distant metastases. Therefore, a total of 16 patients (Group 1) was treated with TT, RT and CHT in various order. Nine patients with distant metastases at diagnosis (Group 2) received CHT; one of them had a disappearance of lung metastases and was then treated by TT and further CHT. Group 3 consisted of 14 elderly patients in poor general conditions; 4 of these received local RT, while the remaining did not receive any treatment. Four complete responses were seen in patients from Group 1, and 1 from Group 2. One patient without distant metastases at diagnosis is alive and free of disease 6 months after TT and adjuvant CHT, and 12 months after diagnosis. Three had long-term survival (14, 24, 27 months) with a disease-free interval of 6-8-10 months. The patient from Group 2 who was treated in a second time by TT is alive without disease after 60 months. Median survival rate was 11 months for Group 1, 5.7 months for Group 2 and 4 months for Group 3. In some patients multimodality treatment (TT, RT and CHT) is associated with increased survival. Nine out of 16 patients, who underwent surgery and complementary treatment, had no local progression. In all but one distant metastases developed, mainly in the lung, during or after post-surgical CHT. The best results were obtained in younger patients with less advanced disease. Early diagnosis is mandatory. Only a few patients responded to CHT, confirming that anaplastic thyroid carcinoma is often resistant to anticancer drugs. Our experience with combination modalities suggests that aggressive and appropriate combinations of RT, TT and CHT may provide some benefit in patients with anaplastic thyroid carcinoma. Preoperative CHT and RT may enhance surgical resectability of the primary tumor.     

Surgery and radiotherapy in vulvar cancer

The majority of patients with vulvar cancer have squamous cell carcinomas (SCC). The cornerstone of the treatment is surgery. Radical vulvectomy with "en bloc" inguinofemoral lymphadenectomy has led to a favorable prognosis but with impressive morbidity. Nowadays, treatment is more individualized with wide local excision with uni- or bilateral inguinofemoral lymphadenectomy via separate incisions as the standard treatment for early stage patients with SCC of the vulva with depth of invasion >1 mm without suspicious groins. In case of more than one intranodal lymph node metastasis and/or extranodal growth, postoperative radiotherapy on the groins and pelvis is warranted. Until now there is a limited role for primary radiotherapy on the vulva and/or groins in early stage disease. The sentinel lymph node (SLN) procedure with the combined technique (preoperative lymphoscintigraphy with a radioactive tracer and intraoperative blue dye) is a promising staging technique for patients with early stage vulvar cancer. The safety of clinical implementation of the SLN procedure and the role of additional histopathological techniques of the SLNs need to be further investigated before its wide-scale application. Patients with advanced vulvar cancer are difficult to treat. One of the problems in patients with locally advanced vulvar cancer is the high incidence of concomitant bulky lymph nodes in the groin(s). Ultraradical surgery in case of resectable disease will lead to impressive morbidity because of the exenterative-type procedure. (Chemo)radiation with or without surgery should be regarded as the first choice for patients with locally advanced vulvar cancer only when primary surgery will necessitate performance of a stoma. Further studies are needed to determine the optimal combined modality treatment in these patients. Due to the fact that vulvar cancer is a rare disease, further clinical studies will only be possible, when international collaborative groups will join forces in order to perform clinical trials, in which different treatment options such as SLN procedure, primary radiotherapy on the groins and multimodality treatment for advanced disease will be investigated.     

Review of squamous premalignant vulvar lesions

Vulvar squamous cell carcinoma (SCC) develops following two different pathways, which have their own premalignant lesions. In the absence of human papilloma virus (HPV), vulvar SCC can develop in a background of lichen sclerosus (LS), differentiated vulvar intraepithelial neoplasia (VIN) or both. The other pathway leading to vulvar SCC is associated with HPV and the HPV-associated premalignancy is usual VIN. In this review we will discuss the history, epidemiology, aetiology, histology, clinical characteristics, treatment options, malignant potential and prevention strategies of the three squamous premalignant vulvar lesions.     

Primary systemic CD30 (Ki-1)-positive anaplastic large cell lymphoma of the adult: sequential intensive treatment with the F-MACHOP regimen (+/- radiotherapy) and autologous bone marrow transplantation

Few series of adult patients with primary systemic CD30 (Ki-1)-positive anaplastic large cell lymphoma (ALCL) are reported in the literature; most of them have been treated with combination chemotherapy (CHT), with only an occasional patient being autotransplanted, mainly after relapsing. The remission rate ranges from 60% to 90%, but relapses are frequent (up to 60%) and precocious (mainly in the first 24 months). The aim of our study was to analyze the outcome of a series of adult patients affected by primary systemic ALCL that were treated at our institution with a sequential intensive therapeutic program including CHT, radiotherapy (RT), and autologous bone marrow transplantation (ABMT). Sixteen consecutive, unselected patients with ALCL were identified. All of them were treated with the 5-fluorouracil, methotrexate, cytosine arabinoside, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP) regimen; 9 of 16 (56.2%) reached a complete remission (CR). In six cases with residual mediastinal disease, involved-field RT was performed, allowing three additional patients to become free of disease. All 16 were then autotransplanted with bone marrow stem cells after conditioning with the cytosine arabinoside, etoposide, cyclophasphamide, and carmustine (BAVC) regimen. A present, 16 of 16 patients are alive and in CR. The actuarial overall survival is 100% at a median of 45.5 months, and the actuarial disease-free survival is 100% at a median of 33.5 months. These data suggest that ALCL can be successfully managed with a sequential intensive treatment (CHT +/- RT + ABMT) that prevents early relapses and projects these patients as long-term survivors.     

Breast cancer and neoadjuvant therapy: any predictive marker?

The majority of patients with breast carcinoma receive chemotherapy as a component of multimodality treatment. Over the past decade, it has become increasingly more common to deliver chemotherapy first, but this has raised new questions within all disciplines of cancer management. However, the effect of cytotoxic treatment cannot be predicted on individually specific basis, then identification of tumor characteristics associated with tumor therapeutic response and outcome is then of great clinical interest. We studied 141 patients at Masaryk Memorial Cancer Institute, who received neoadjuvant chemotherapy and/or chemotherapy + radiotherapy (CHT/CHT+RT) between 1994-2002. Tumor samples were taken prior to and after neoadjuvant therapy. We quantified the response to therapy pathologically and determined histological and molecular tumor characteristics (steroid receptors, CEA, Ca 15-3). In addition to therapeutic response as immediate outcome, event free survival (EFS) was examined as more complex primary end-point of the study. Complete remission (CR) has been achieved in 6.5%, partial remission (PR) in 49.6%, stable disease (SD) in 26.2% and progression disease (PD) in 17.7% patients. Patients were divided into two groups according to the result of neoadjuvant therapy--responders (CR+PR+SD, who successfully underwent surgery), and risk group (patients with SD or PD, who could not undergo surgery). Responders to neoadjuvant CHT/CHT+RT regimens reached statistically significant better EFS than non-responders, low tumor size (T2) and stage (II) categories were confirmed as additional predictive factors not only for EFS but for therapeutic response as well. The study primarily examined predictive power of tumor markers as CEA, Ca 15-3, and steroid receptors (ER/PR) and searched for their role in the prospective evaluation of neoadjuvant therapy. We evaluated these factors as potential predictors of EFS, independent in predictive power on therapeutic response to neoadjuvant therapy. Diagnostically valuable cut off points were proposed in ROC analysis for all these markers. Responders to the neoadjuvant therapy with Ca 15-3 <23.0 kU/l, CEA <5.0 mg/l, estrogen receptors (ER) >5.0 fmol/mg or both estrogen /progesterone receptors (ER/PR) positive had statistically significantly better EFS in comparison to patients with Ca 15-3 >23.0 kU/l, CEA >5.0 mg/l, ER <5.0 fmol/mg, or other cases than patients double positive in ER/PR. Marker Ca 15-3 revealed significant predictive power even within the group of non- responders, these patients with Ca 15-3 <23.0 kU/l had better EFS as compared to patients with Ca 15-3 >23.0 kU/l. Tumor size and low stage proved predictive value for immediate response to neoadjuvant therapy. Risk parameters for neoadjuvant therapy were T4, stage III, namely if RT was necessary. Therapeutic response to neoadjuvant therapy was independent on investigated molecular parameters, but there was strong predictive association of Ca 15-3, CEA and ER/PR receptors with event free survival development. Diagnostically valuable cut-off points were proposed and validated for sensitivity and specificity in ROC analysis.     

老年妇女外阴癌及外阴营养不良与p53突变及人乳头瘤病毒感染的相关性

目的：探讨老年妇女外阴癌组织中p53表达及人乳头瘤病毒（HPV）感染与外阴癌发生及临床发展的关系。方法：应用免疫组化法检测老年妇女外阴鳞状细胞癌（外阴癌）68例及老年妇女外阴营养不良38例病例蜡块包埋组织中p53,HPV的表达情况，并选用15例外阴正常皮肤作为对照。结果：p53,HPV在老年妇女外阴癌组织中阳性表达率分别为54．4％，45．6％，老年妇女外阴营养不良组织中为18．4％，55．3％，老年妇女正常外阴皮肤无阳性表达。外阴癌与外阴营养不良，正常对照比较差异有显著性（分别为P＜0．05及P＜0．01）。结论：老年妇女外阴癌组织中p53,HPV阳性表达率较高。p53突变在老年妇女外阴癌的发生过程中起重要作用，高危型HPV的感染促进外阴癌的发生。     

Clinical characteristics, treatment outcome and survival of 36 adult patients with primary anaplastic large cell lymphoma. Gruppo Italiano per lo Studio dei Linfomi (GISL).

BACKGROUND AND OBJECTIVE: Although in recent years anaplastic large-cell lymphoma (ALCL) has emerged as a distinct clinico-pathological entity, a gold standard for treatment has still not been defined. Goals of our histologic, phenotypic and clinical study were to present clinical findings, treatment outcome and survival rates of a small, but highly homogeneously treated, series of patients. DESIGN AND METHODS: From April 1991, 36 newly diagnosed adult patients with systemic ALCL CD30+, entered a prospective non-randomized trial in one of the institutions participating in a GISL (Gruppo Italiano per lo studio dei Linfomi) study and were treated with a MOPP/EBV/CAD hybrid scheme. Chemotherapy (CHT) was administered every 28 days, for a total of 6 cycles. After CHT, 19 patients received radiation therapy (RT) to the site of previously involved fields. Kaplan and Meier and log-rank tests were used for statistical analysis. RESULTS: The overall complete remission rate was 78%, the partial remission rate was 6%. The overall survival rate at 74 months was 69%. No statistically significant differences in response or survival rates were noted comparing ALCL-HL and -CT subgroups, T+ Null- and B- subtypes, or ALCL-HL and -CT, with different phenotypes. In the analysis of patients with T+ Null phenotype treated with CHT+RT in comparison with B-ALCL patients who had the same treatment, we observed statistically significant differences in the survival rate (p=0.048). No prognostic factors predictive of response or survival were identified. INTERPRETATION AND CONCLUSIONS: Our results show that using MOPP/ABV/CAD the results, in terms of remission rate and survival, are similar to those obtained with 3rd generation CHT regimens. The diagnosis of T and Null ALCL is the most important prognostic factor, because it is associated with a very good survival, even in patients with a high prognostic index. Finally, we believe that longer follow-ups are needed to evaluate long-term survival and toxicity with different treatments.     

Endocrine care of transpeople part I. A review of cross‐sex hormonal treatments,outcomes and adverse effects in transmen

Gender dysphoria (GD) is characterized by discomfort with the assigned or birth gender and the urge to live as a member of the desired sex. The goal of medical and surgical treatment is to improve the well‐being and quality of life of transpeople. The acquisition of phenotypic features of the desired gender requires the use of cross‐sex hormonal therapy (CHT). Adult transmen are treated with testosterone to induce virilization. In adolescents with severe and persistent GD, consideration can be given to arresting puberty at Tanner Stage II and if dysphoria persists, CHT is generally started after 16 years of age. Currently available short‐ and long‐term safety studies suggest that CHT is reasonably safe in transmen. Monitoring of transmen should be more frequent during the first year of cross‐sex hormone administration reducing to once or twice per year thereafter. Long‐term monitoring after sex reassignment surgery (SRS) includes annual check‐ups as are carried out for natal hypogonadal men. In elderly transmen, special attention should be paid to haematocrit in particular. Screening for breast and cervical cancer should be continued in transmen not undergoing SRS.     

Treatment results of aggressive B non-Hodgkin's lymphoma in advanced age considering comorbidity

The aim of this retrospective single institution study was to investigate the long-term outcome of sequential chemotherapy (CHT) and radiotherapy (RT) in patients >/= 70 years old, considering the International Prognostic Index (IPI) for high-grade non-Hodgkin's lymphoma (NHL) and comorbidity. The study involved 106 patients aged 70 years and above, treated between 1986 and 1998, for diffuse large B-cell NHL (DLBCL); 57% had localized disease (stage I or II) and 43% had advanced disease (stage III or IV). All patients received four to six cycles of CHOP (cyclophosphamide, hydroxy-daunorubicin, oncovin, prednisone) CHT at 14-21 d intervals, followed in 69 cases by extended-field or involved-field RT. Complete response rate was 65%; overall survival probability at 5 years was 41% in all stages. Five-year survival was 62% in patients with localized and 12% in advanced disease. There were 3% treatment-related deaths. The 5-year survival rate was 70% in patients with IPI low risk, 46% with low-intermediate risk, 28% with high-intermediate risk and 0% with high risk. Patients with cardiac problems and advanced disease were more susceptible to treatment-related toxicity. Patients with hypertension showed a high rate of vinca alkaloid-associated polyneuropathy. Most patients with localized DLBCL achieved long-term remission after CHT and RT regimens despite advanced age and frequent comorbidities. Advanced disease increased the risk for treatment-related complications and efficacy of treatment seemed limited.     

Old and new perspectives in the management of high-risk, locally advanced or recurrent, and metastatic vulvar cancer

During the last decades there has been a continuing evolution in the surgical approach of squamous cell carcinoma of the vulva that has been traditionally treated with radical vulvectomy and bilateral inguinal-femoral lymphadenectomy. Patients with T1 tumour are usually treated with radical local excision, if the lesion is unifocal and the remainder of the vulva is normal. Patients with T1a disease have no risk of groin metastases and do not need lymphadenectomy, whereas those with T1b disease need ipsilateral inguinal-femoral lymphadenectomy if the lesion is lateral, and bilateral lymphadenectomy if the lesion is midline. Modifications of the surgical technique of deep femoral lymphadenectomy and the mapping of sentinel node can offer new interesting therapeutic perspectives. Postoperative adjuvant pelvic and groin irradiation is warranted for patients with two or more or macroscopically involved groin nodes. Locally advanced squamous cell carcinoma of the vulva has been long surgically treated with en-block radical vulvectomy and bilateral inguinal-femoral lymphadenectomy plus partial resection of urethra, vagina or anum, or by exenteration, with severe postsurgical complications, poor quality of life, and unsatisfactory survival rates. 5-Fluorouracil [5-FU] or 5-FU- and cisplatin-based chemotherapy concurrent with irradiation followed by tailored surgery represents an attractive therapeutic option for advanced disease, planned to avoid such ultra-radical surgical procedures and, hopefully, to improve patient outcome. Chemotherapy has also been used in neoadjuvant setting, with contrasting and generally unsatisfactory results, and in palliative treatment of patients with distant metastases. Surgery is the primary treatment also for vulvar malignancies other than squamous cell carcinoma, whereas the clinical usefulness of adjuvant irradiation or chemotherapy is still to be defined. Primary chemoradiation can be also used for advanced carcinoma of the Bartholin gland or for advanced adenocarcinoma associated with extramammary Paget's disease. The drugs used for chemotherapy of metastatic melanomas or sarcomas of the vulva are the same employed for the melanomas or sarcomas developed in other sites.     

Crohn's disease of the vulva

Crohn's disease (CD) of the vulva is a rare, yet under recognized condition. Fistulae arising from the digestive tract account for the greater part of genital lesions in CD. However, cutaneous so-called metastatic lesions of the vulva have been reported in the literature. They are clinically challenging for gastroenterologists as well as for gynecologists, with numerous differential diagnoses, especially among venereal diseases, and require a multidisciplinary approach. The most frequently observed features of the disease are labial swelling, vulvar ulcers, and hypertrophic lesions. Biopsy samples for histological study are mandatory, in order to establish the diagnosis of vulvar CD. Treatment options include oral prolonged courses of metronidazole and systemic immunosuppressive therapy such as corticosteroids and azathioprine, with promising data published on the efficacy of infliximab. Surgery remains restricted to medical treatment failures or resection of unsightly lesions. Prospective studies or case series with long follow-up data are still missing to guide the treatment of this condition.     

Old and new perspectives in the management of high-risk,locally advanced or recurrent,and metastatic vulvar cancer

During the last decades there has been a continuing evolution in the surgical approach of squamous cell carcinoma of the vulva that has been traditionally treated with radical vulvectomy and bilateral inguinal-femoral lymphadenectomy. Patients with T1 tumour are usually treated with radical local excision, if the lesion is unifocal and the remainder of the vulva is normal. Patients with T1a disease have no risk of groin metastases and do not need lymphadenectomy, whereas those with T1b disease need ipsilateral inguinal-femoral lymphadenectomy if the lesion is lateral, and bilateral lymphadenectomy if the lesion is midline. Modifications of the surgical technique of deep femoral lymphadenectomy and the mapping of sentinel node can offer new interesting therapeutic perspectives. Postoperative adjuvant pelvic and groin irradiation is warranted for patients with two or more or macroscopically involved groin nodes. Locally advanced squamous cell carcinoma of the vulva has been long surgically treated with en-block radical vulvectomy and bilateral inguinal-femoral lymphadenectomy plus partial resection of urethra, vagina or anum, or by exenteration, with severe postsurgical complications, poor quality of life, and unsatisfactory survival rates. 5-Fluorouracil [5-FU] or 5-FU- and cisplatin-based chemotherapy concurrent with irradiation followed by tailored surgery represents an attractive therapeutic option for advanced disease, planned to avoid such ultra-radical surgical procedures and, hopefully, to improve patient outcome. Chemotherapy has also been used in neoadjuvant setting, with contrasting and generally unsatisfactory results, and in palliative treatment of patients with distant metastases. Surgery is the primary treatment also for vulvar malignancies other than squamous cell carcinoma, whereas the clinical usefulness of adjuvant irradiation or chemotherapy is still to be defined. Primary chemoradiation can be also used for advanced carcinoma of the Bartholin gland or for advanced adenocarcinoma associated with extramammary Paget's disease. The drugs used for chemotherapy of metastatic melanomas or sarcomas of the vulva are the same employed for the melanomas or sarcomas developed in other sites.     

Use of tamoxifen in the treatment of Riedel's thyroiditis: report of a case

Treatment of Riedel's thyroiditis (RT) consists of surgery in cases of local limited fibrosis. In most cases, however, it is required the use of anti-inflammatory agents like glucocorticoids or, in those who fail to respond or relapse, tamoxifen can be useful. We report a case of RT in a 55-year-old black woman associated with hypothyroidism and hypoparathyroidism. We evaluated the treatment with tamoxifen, 20 mg twice a day, for eleven months. After sixty days of therapy, patient had no compressive symptoms previously presented. However, in a follow-up of eleven months, there was little objective improvement by regular ultrasonography and computed tomography of the cervical region. Tamoxifen can be useful in RT, mainly when glucocorticoids are not indicated. The ideal duration of this therapy remains to be established.     

Effects of combined immunotherapy with levamisole and Bacillus Calmette-Guérin on immunocompetence of patients with squamous cell carcinoma of the cervix, head and neck, and lung undergoing radiation therapy.

Patients with squamous cell carcinoma of the head and neck, squamous cell carcinoma of the cervix, and lung carcinoma were treated with radiation therapy (RT) prior to being randomly assigned either to a group receiving no further treatment or to a group treated with combined adjuvant immunotherapy (bacillus Calmette-Guérin and levamisole). A battery of in vitro immunologic evaluations in addition to skin tests was used to evaluate these patients prior to RT, immediately following RT, and at regular intervals thereafter. Mean percentages and levels of circulating T lymphocytes were significantly lower in all three types of patients prior to RT than in normal healthy controls. B-lymphocyte percentages and levels, however, were not significantly different from controls except for lower B-cell levels in the lung group. Following completion of RT, circulating levels of both T and B lymphocytes were significantly lower than pretreatment values although the percentages were not significantly changed. Mitogenic responses of patient lymphocytes to both phytohemagglutinin and pokeweed mitogen were significantly lower prior to RT than were healthy control responses. A further depression of blastogenesis following RT was statistically significant. Preliminary data at intervals following RT indicate a gradual recovery of depressed immune parameters (T- and B-lymphocyte levels and mitogenic responses) both in patients treated with adjuvant immunotherapy and in those receiving no further treatment. Although not statistically significant in preliminary data, there is a suggestion that recovery of these immune parameters is slower in the group receiving immunotherapy. Plasma sialic acid levels were elevated in patients when compared to healthy controls and remained elevated throughout the study with little fluctuation. Lymphocyte cytotoxic activity against tumor target cells was variably affected by RT, but was generally increased at 8 weeks following RT when compared to previous values.     

Palliative Hypofractionated Radiotherapy For Non-small-cell Lung Cancer (NSCLC) Patients Previously Treated By Induction Chemotherapy

Aim

To investigate the effectiveness and toxicity of radiotherapy (RT) given as 17 Gy in 2 fractions, in patients with locally advanced non-small-cell lung cancer (NSCLC) previously treated by platinum-based chemotherapy (CHT) and the impact of total tumor volume (TTV) on symptoms control.

Materials and methods

Patients with inoperable NSCLC resistant to induction platinum-based CHT, who developed symptoms during or just after radiotherapy, were treated by 17 Gy in two fractions one week apart. In 12/28 patients a minimal response (up to 20% of TTV) and in 16/28 a stable or locally progressive disease had been recorded after induction CHT. In 26/28 patients, symptoms were present during-after CHT and before RT. The prognostic significance of pre-RT TTV on symptoms control and patients survival was also examined.

Results

We report on 28 patients. Response rates for the four main symptoms were: cough 13/19 (68%), haemoptysis 9/10 (90%), pain 8/14 (57%) and dyspnoea 5/13 (38%). Hematologic and local-thoracic toxicities were minimal. The median survival from the beginning of RT, for the whole group of patients was 9 months (95% CI:3.7-14.3), while for those patients with TTV<120 cc it was 12 months, and for those with TTV 120cc, it was 5.2 months. TTV was not suggested to influence symptoms control rate.

Conclusion

The two-fraction radiotherapy course is safe and effective in palliation of symptomatic non-small-cell lung cancer patients non-responding to induction CHT. Present data suggests that the TTV may influence survival time.     

Breast cancer in the elderly: the role of adjuvant radiation therapy

PURPOSE: To evaluate available data on breast conserving surgery (BCS) with or without radiation therapy (RT), and alternative options (e.g. Tamoxifen alone) (Tam), focusing specifically on the older patients. METHODS AND MATERIALS: The MEDLINE was searched for the terms elderly, BCS, adjuvant/postoperative RT, Tamoxifen, and randomized trials from 1992 to 2002. RESULTS: Authors reviewed papers of general interest on the elderly and breast cancer (BC), meta-analysis, randomized trials on BCS+/-RT and Tam+/-surgery without RT, retrospective non-randomized trials, and reported on prognostic factors for local recurrence in BCS alone, including biomarkers, attempts made to define a low-risk group, and methods of modification of the current, protracted standard adjuvant RT course. CONCLUSIONS: Postoperative RT after BCS has a firm rationale; in current clinical practice, if the BCS+RT is medically appropriate and the patient shares the choice, after a full information of the available options and their implications, it is clinically sound to propose this approach. However, there is controversy whether a subgroup of elderly patients could be safely spared: in this setting a randomized trial is clearly warranted.     

The current role of transcranial surgery in the management of pituitary adenomas

The aim of this study was to determine the factors influencing the use of a transcranial (TC) approach in pituitary adenomas and suggest a decision-making tree for the surgical strategy. The data for 23 (4.6 %) patients who underwent TC surgery from amongst 494 pituitary adenomas were retrospectively analyzed. Eight factors on magnetic resonance imaging (MRI) that could predict a difficult transsphenoidal (TS) surgery were noted. Adverse findings at TS surgery leading to a 2nd stage TC surgery were documented. Eighteen of the 23 cases were giant adenomas. Thirteen patients underwent TC surgery alone or as an initial approach when combined with TS while 10 underwent 2nd stage TC surgery following a TS approach. Most cases in the first group had 3 or more radiological factors in combination with a small sella. The 2nd group had higher sellar tumor volumes and fewer unfavourable radiological factors that led to the initial use of the TS approach. A hard, fibrous consistency or a significant residue obscured from the surgeon’s view, and difficulty in hemostasis were additional factors prompting the use of a TC approach. Tumor excision ≥90 % could be achieved in 13 cases (56.5 %). Post-operative RT was administered in 12 patients. There were 2 deaths (8.7 %) and the major morbidity rate was 43 %. Despite advances in endoscopic surgery the TC approach may be required in 5 % of cases. A study of the preoperative MRI for factors that predict difficulty with the TS approach might encourage the surgeon to consider a TC surgery either as an initial approach or combined with a TS surgery.