Interobserver variability of clinical target volume delineation in soft-tissue sarcomas.

PURPOSE: The present observational study reports the results of a multi-institutional dummy-run designed to estimate the consistency of interobserver variability in clinical target volume delineation in two different cases of soft-tissue sarcomas in which postoperative and preoperative radiotherapy were prescribed, respectively. The purpose of this work was to quantify interobserver variability in routine clinical practice. PATIENTS AND METHODS: Two different cases of soft-tissues sarcomas were chosen: a case of postoperative and a case of preoperative radiation therapy. Participating centres were requested to delineate clinical target volumes according to their experience in both cases. Descriptive statistic was calculated for each variable (volume, diameters) separately for two cases. Box-whiskers plots were used for presentation of clinical target volume. A Shapiro-Wilk's test was performed to evaluate the departures from normality distribution for each variable. The comparison between relative variations of diameters was evaluated using the Student's t test. RESULTS: Several variations affecting both volumes and diameters were observed. Main variations were observed in the craniocaudal and laterolateral diameters. Each case showed similar dispersion, indicating a lack of reproducibility in volumes definition. CONCLUSIONS: This observational study highlighted that, in the absence of specific instructions or guidelines, the interobserver variability can be significant both in postoperative and preoperative radiotherapy of soft-tissue sarcomas.

Diffusion-weighted magnetic resonance for prediction of response after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: preliminary results of a monoinstitutional prospective study.

PURPOSE: To evaluate diffusion-weighted imaging (DWI) for assessment of treatment response in locally advanced rectal cancer (LARC) 8 weeks after neoadjuvant chemoradiotherapy (CRT). METHODS AND MATERIALS: A total of 28 patients with LARC underwent magnetic resonance imaging (MRI) prior to and 8 weeks after CRT. Tumor volume (TV) was calculated on T2-weighted MRI scans as well as the apparent diffusion coefficient (ADC) was calculated using Echo-planar DWI-sequences. All data were correlated to surgical results and histopathologic tumor regression grade (TRG), according to Mandard's classification. Post-treatment difference ADC (%ΔADC) and TV (%ΔTV) changes at 8 weeks were compared complete response (CR; TRG1) and non-complete response tumors (non-CR; TRG2-5). RESULTS: The mean % ADC increase of CR group was significantly higher compared to non-CR group (77.2 ± 54.63% vs. 36.0 ± 29.44%; p = 0.05). Conversely, the mean % TV reduction did not significantly differ in CR group from non-CR group (73.7% vs. 63.77%; p = 0.21). Accordingly, the diagnostic accuracy of the mean % ADC increase to discriminate CR from non-CR group was significantly higher than that of the mean % TV reduction (0.913 vs. 0.658; p = 0.022). No correlation was found between mean % TV reduction and TRG (rho = 0.22; p = 0.3037), whereas a negative correlation between mean % ADC increase and TRG was recorded (r = -0.69; p = 0.006). CONCLUSION: The mean % ADC increase appears to be a reliable tool to differentiate CR from non-CR after CRT in patients with LARC.

The role of radiotherapy in the management of elderly cancer patients in light of the GROG experience.

60-70% of all cancers will develop in individuals aged 65 and over during this century. Radiation therapy will play a major role in the treatment of cancer, especially in the elderly. The Italian Geriatric Oncology Group (GROG) in 1994 started a number of prospective studies to assess the characteristics of each elderly cancer patient referred to the radiotherapy centers (age, gender, performance status, comorbidity, ADL, family status) and the main features of the tumor in that patient. Based on the obtained results, the role of radiotherapy is underlined and future perspectives are identified.

Quality of life in elderly cancer patients.

Increasing age is a major risk factor for developing cancer and the number of older people is rapidly expanding. Therefore, cancer in the geriatric population is becoming an emerging problem. Older patients are extremely heterogeneous. Instruments collecting information related to comorbidity and disability, (which have both been demonstrated to affect the survival of elderly patients) may help treatment decision. The G.I.O.Ger (Gruppo Italiano di Oncologia Geriatrica) has validated a Comprehensive Geriatric Assessment (CGA) scale for geriatric cancer patients, and we recommend its use in clinical practice. Our findings suggest that cancer adversely affects physical performance and psychological status less than other comorbidities. Many aspects of physical limitations are not totally recognised by performance status, in particular those aspects of daily life that require instrumental activities and that may affect adherence to diagnostic or therapeutic protocols. Quality of life as a main objective in the management of elderly cancer patients is now recognized by many clinicians. In clinical practice. quality of life means maintenance of function and symptom control, and quality-of-life instruments rated by the patient rather than by clinicians should be preferred. Whether it is preferable to use cancer-specific or generic instruments is an ongoing debate.

Head and neck cancer: new trends in research and clinical practice.

Head and neck cancer represents an interesting subject of research in the third millennium. Apart from basic research (molecular biology, genic therapies etc.) which it shares with other neoplasms, a number of studies are in progress in the field of clinical research. In particular trials of combined radiation and chemotherapy with one or several drugs are being carried out and they will certainly provide definitive results in the field of clinical application. Further acquisitions will be provided by the studies on non conventional dose fractionation and the application of intensity modulated radiotherapy. Finally, the first studies on chemoprevention in patients with malignant or precancerous lesions of the head and neck will be soon concluded.

Breast cancer: new trends of clinical research.

In breast physiopathology, in spite of the crop of information and clinical studies, a number of questions are still unsolved. The adequacy of research sources and the transmission of information to clinical practice through consistent and validated efficacy evidences are required to ensure the treatment quality. In this article the different specialist approaches and the main themes debated in the interdisciplinary approach to breast cancer are considered: the genetical risk factors, the role of diagnostic imaging, the mapping and assessment of sentinel lymph node, the role of nodal radiation therapy following mastectomy.

The impact of the new organization on the management of breast cancer.

The radical change in the health care service now going on for some years requires the commitment of medical specialists, as well as the acquisition of an adequate knowledge of the economic implications associated to the therapeutic choice. Among primary objectives of health care management in the field of breast cancer, the best cost-effective strategy and the rationalization and standardization of diagnostic and therapeutic approaches, should be identified. Problems related to breast cancer are examined for effective, efficient and economic optimization.

Morphometric prognostic index in breast cancer.

OBJECTIVE: To assess the ability of the morphometric prognostic index (MPI) in predicting clinical outcome in a group of breast cancer patients with short-term follow-up and to assess the relationship between MPI and other prognosticators. STUDY DESIGN: The study group consisted of 63 cases of breast cancer. Follow-up data were available for 48 patients. MPI values were calculated, and degree of nuclear and tubular differentiation was investigated in each tumor. S-phase fraction (SPF), estrogen and progesterone receptors were also studied. RESULTS: The group of patients with MPI values < 0.60 had percent values of disease-free survival significantly higher than did those with MPI values > or = 0.60. Furthermore, significant direct correlations were found between MPI and degree of nuclear atypia and between MPI and SPF. Significant inverse relationships were found between MPI and tumor progesterone receptor levels and between MPI and degree of histologic tubular differentiation. CONCLUSION: The validity of MPI as a prognosticator in breast cancer was confirmed, even in a limited number of patients observed in short-term follow-up. MPI seems to be a reliable and economical prognosticator in selecting breast cancer patients for adjuvant chemotherapy.

[Supportive therapy in oncology]. / Le terapie di supporto in oncologia.

The current trend towards a more intensive cancer treatment is possible thanks to the availability of a really important and effective supportive care. It is our opinion that it would be essential for the junior staff in oncology, for the practitioners, but also for the knowledge of anyone contributing in different ways to give the cancer treatment, to have reference points to give also the best supportive care. With this aim we thought to start a study, in Italy, to investigate, first, which is the supportive care used in the most common acute toxicities during or immediately after cancer therapy. We decided to begin with a survey addressed to hematologists, medical oncologists, radiotherapists; 105 centers were contacted. In order to have a high number of people able to answer to different clinical questions we decided to use Internet to communicate with participating centers without moving people. The final goal of the project is to formulate guidelines in supportive care, but also to promote the use of Internet as much as possible in the medical world with the aim to make easier every kind of communication and exchange of information.

Supportive care in radiotherapy: a review.

The normal tissue tolerance and the related early side effects represent the main constraint on the total radiation dose which can be administered to the target volume. The most common disorders during radiotherapy or chemo-radiotherapy are summarized in this review. Since in the recent years great advances have been made towards the improvement of acute tolerance, practically every adverse symptoms can be controlled or lowered with an adequate treatment. Some suggestions are reported in order to prevent or lower the degree and the incidence of major complications, specifically mucositis-related symptoms like stomatitis, diarrhea, cystitis. Possibly, a multicenter effort is to be made in order to optimize the quality of supportive care for irradiated patients in all radiation therapy centers.

Chemoradiotherapy with carboplatin in continuous infusion in the locoregional control of advanced head and neck cancer.

Because of the difficulty to achieve and maintain locoregional control in head and neck cancer, many clinical trials were focused on the addition of chemotherapy to locoregional treatments in advanced head and neck cancer patients. In particular, concomitant chemoradiotherapy resulted in high response rate and improved local control, sometimes with increased toxicity. In the effort to improve local control a phase II study on chemoradiotherapy with carboplatin in prolonged continuous infusion for 14 days (420 mg/m2 total dose) during standard radiotherapy, was performed. 45 patients were evaluable for response: CR 62.5% (global response 96%). After a mean follow-up of 48 months 9/28 patients with CR were still alive with no evidence of disease; two additional patients were alive but with locoregional disease. As for deceased patients, one died from non-tumor related causes, 13 from locoregional disease and 2 for metastatic disease. If the entire population of Crs is analyzed, it is observed that 13 patients (46.5% of CRs and 29% of the entire series) maintained a durable locoregional control. In most patients recurrence was detectable both in the primary tumor and in the neck.

Local control in breast cancer: impact on survival.

The role of radiotherapy in breast cancer is examined, based on a review of literature. Its impact on survival is discussed in the framework of a multidisciplinary treatment of the disease.

[Supportive care in oncology]. / Le terapie di supporto in oncologia.

It is extremely important to deliver treatments, both in medical oncology and in radiation oncology, in compliance with the due dose intensity, in order to achieve the best results in terms of clinical response and local control and, often, also in terms of survival. Supportive care is one of the tools for the achievement of this goal, permitting the delivery of aggressive therapies and the improvement of Quality of Life. It is the aim of the Tsonc study to evaluate what the main therapeutic trend is, on the ground of a survey performed in 105 medical oncology, radiation oncology, and haematology centres. For this assessment the WHO/INH and RTOG common toxicity criteria were adopted, even knowing that these score systems had been developed for reporting acute/subacute toxicity and not to choose the therapeutic approach. However, these scales give us the possibility to refer to highly validated systems and provide participants with a common language. Thirty-two items of toxicity were listed, and each item included 2 to 4 degrees of severity so to report supportive care accordingly. The present paper reports the criteria of choice of the scales and symptoms and the schedule of the queries.

Italian Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group Trials. GROCTA Trials.

The first GROCTA trial compared 5-year tamoxifen treatment to ten chemotherapy cycles in a group of 504 pre-/post-menopausal, node-positive, ER-positive breast cancer patients. This study also included an arm combining tamoxifen with chemotherapy. Fifteen-year results showed no difference between tamoxifen and tamoxifen plus chemotherapy, while both treatments were significantly superior to chemotherapy alone. A confirmatory study (GROCTA 02) was performed in 244 pre-/perimenopausal patients by comparing 5 years of tamoxifen treatment (plus 2 years of goserelin) to six CMF cycles. No difference has emerged so far between the tamoxifen and CMF arms at a median follow-up time of 62 months. Post-menopausal women were scheduled to receive 3 years of tamoxifen treatment and then to be randomly allocated to further 2 years of tamoxifen or to 2 years of low-dose aminoglutethimide (GROCTA 04B). So far 662 patients have been entered, 375 of whom have been randomized to tamoxifen (n = 188) or aminoglutethimide (n = 187). Preliminary results (median follow-up time 32 months) show no major difference in patients' outcome. A new trial (ITA trial) with a similar design but employing anastrozole in place of aminoglutethimide has been activated in 1998. The GROCTA 03 study investigated the potential superiority of alternating adjuvant chemotherapy over standard CMF. This study, which included 107 node-positive ER-negative pre-menopausal women, was prematurely closed because more patients allocated to the triple alternated chemotherapy appeared to have relapsed and died at the first interim analysis. The use of high-dose chemotherapy (HDC) was explored by the GROCTA 06 trial which included 53 patients with ten or more involved nodes and a maximum age of 55 years. These patients were scheduled to receive three standard CEF cycles followed by one cycle of HDC (cyclophosphamide 5 g/m2; etoposide 1.5 g/m2; cisplatin 150 mg/m2) without any form of bone marrow rescue. This HDC program proved to be feasible but was not superior to CMF-based chemotherapy we had previously employed in a comparable group of patients in previous GROCTA trials. These findings prompted us to explore new HDC programmes with the use of peripheral stem cell support and in addition the possible value of new drugs such as Taxol and vinorelbine. New-generation trials will also explore the value of new prognostic indicators such as tumor proliferative activity, which are prospectively used to allocate patients to different treatment options.

Preoperative radiotherapy in the conservative treatment for breast cancer.

Aim of this study was to evaluate the feasibility, therapeutic effectiveness and toxicity of a non conventional radiation therapy (180 cGy twice a day for a total dose of 36 Gy in 2 weeks in the treatment of breast cancer inoperable with conservative surgery as first choice. Ten patients were studied. Results were as follows: complete response: 20%, partial response: 70%; no change: 10%. Acute toxicity was negligible and late toxicity, after a mean 46-month follow-up, was practically absent; the cosmetic result was definitely good. The radiobiology and kinetic features of breast cancer indicate that the potential of accelerated treatment should be further explored, this fractionation being suitable for optimal combined modality treatment with preoperative chemotherapy.

Organ preservation with radiochemotherapy in locally advanced bladder cancer.

Bladder cancer is frequent in Western countries and predominantly affects males (ratio: 3:1). In 15-25% of cases there is muscular wall invasion. Treatment of > T1 tumors is radical cystectomy with or without preoperative radiotherapy. In T2 there is 60% survival at 5 years, 40% in T3. Exclusive radiotherapy used to prevent radical cystectomy has lower survival rates in T2 (30-40% at 5 years) as well as in T3 (20% at 5 years). Recently, concomitant radiotherapy and chemotherapy has been introduced again to prevent demolitive surgery. Results are similar or slightly superior than those of surgery alone. In our experience with radiotherapy 180 cGy daily for a total dose of 64 Gy in combination with fluorouracil in locally advanced tumors 40% bladder preservation was achieved.

Combined radiochemotherapy for organ preservation in head and neck cancer: review of literature and personal experience.

Combined radiochemotherapy is the most common method aimed at improving the rate of clinical response in advanced head and neck cancer. Complete clinical remission may correspond to a significant percentage in organ and/or function preservation. In 1992 a protocol of concomitant radiochemotherapy with continuous infusion of carboplatin for 14 consecutive days at the daily dose of 30 mg/m2 and concomitant radiotherapy with conventional fractionation (1.8 Gy to a total 65-70Gy) was started. Over a 3-year period, 56 patients with advanced head and neck cancer, were treated. In view of organ preservation, 26 patients of this series, though with considerable extent of the disease at diagnosis, were considered candidates for radical surgery: oral cavity 9 patients; oropharynx 9 patients; larynx/hypopharynx 8 patients. A single patient was stage I (hypopharynx); most patients were stage III (7) and IV (17 = 65%); T4 20%, N3 23%. 17/20 patients (70%) showed complete clinical response, 6 partial clinical response with a single non responder (overall response 95%). A patient underwent total glossectomy followed by local recurrence and another patient underwent pharyngolaryngectomy also followed by recurrence. After a mean follow-up from 22 to 60 months, 9 patients were still free of disease (37.5%). Median duration of complete response was 25.6 months. Overall median survival was 26.7 months: 38 months in responders. 2-year survival of patients with complete response was 59%. As for organ preservation, at present 6 over 18 patients (33%) with tumor of the oral cavity or oropharynx and 3 patients with tumors of larynx/hypopharynx have preserved organ and function. As for complete responders, 54.5% of those with tumors of oral cavity or oropharynx and 50% of those with tumors of larynx/hypopharynx, have preserved anatomy and function after at least 2-year follow-up. To-date, in follow-up controls relevant late toxicity has not been observed, showing that to the positive anatomical result corresponds the functional preservation of single structures.

[Comparison between measured and computed absorbed dose values in the tangential treatment of the breast]. / Confronto tra i valori misurati e calcolati della dose assorbita nel trattamento tangenziale della mammella.

The calculated absorbed dose values to the reference point of the breast tangential irradiation, obtained by 2-dimensional (2D) Treatment Planning Systems (TPS), were compared with the measured absorbed dose values obtained with a ionization chamber in an anthropomorphic phantom treated with two opposed photon beams of 60Co, 6 MV and 10 MV. This comparison was aimed at assessing the 2D algorithm dose overestimation due to the effect of missing tissue in the irradiated field. The ratio between the computed dose, Dc, and the measured dose, Dm, reached 1.08 for 60Co beams and 1.04 for X-ray beams of linacs. The Clarkson method gives an adequate correction factor for the calculated absorbed dose value in the reference point. The portal films of some patients were studied to estimate the correction factor for the treatment time or monitor units evaluated by TPS using tomographic breast central plane. The values of the correction factors reached 1.10 for 60Co photon beams and 1.04 for X-ray beams. The measurements were carried out with TLDs positioned in the central plane of the breast, covered by a special bolus, of a second anthropomorphic phantom. The dose homogeneity as well as the accuracy of the relative computed dose values in the breast phantom irradiated with 10 MV X-ray beams were assessed.

Radiotherapy in the elderly with lung carcinoma: the experience of the Italian "Geriatric Radiation Oncology Group".

One hundred ninety-six patients aged > or = 70 years, with non small-cell lung carcinoma and no evidence of metastasis on staging, observed over a 6-month period in 20 Italian Radiotherapy Centers, were analyzed in order to assess indications for treatment, tolerance of radiotherapy (assessed in terms of completion of planned doses and toxicity), and quality of life using the Performance Status and a concise activity of life test. Of the 196 patients studied in 20 Italian Centers, 182 (98%) underwent radiotherapy, 109(60%) of whom with radical intent and 73 (40%) with palliative intent. Of 179 assessable patients undergoing radiation treatment, 163 (91%) completed the treatment as originally planned. Of the 64 assessable patients who completed palliative radiotherapy, relief of symptoms was observed in a percentage ranging from 78% to 86%. Analysis of parameters assessing the quality of life, showed no significant differences in general and functional conditions, as assessed before and upon completion of radiotherapy.