Tumori Journal

To provide model-based estimates of all cancers patient survival in Italy and in Italian large geographical areas (North-West, North-East, Center, South), where only partial coverage of cancer registries data is available, and to describe them in terms of time trends. Moreover, to measure the degree of representativeness of cancer patient survival obtained from Italian cancer registries data.

Relative survival in the four main Italian geographical areas was estimated by a parametric mixture model belonging to the class of “cure” survival models. Data used are from Italian cancer registries, stratified by sex, period of diagnosis and age. The Italian national survival was obtained as a weighted average of these area-specific estimates, with weights proportional to the number of estimated incident cases in every area. The model takes into account also differences in survival temporal trends between the areas.

Relative survival for all cancers combined in Italian patients diagnosed in 1990-1994 was estimated to be higher in women (53%) than in men (38%) at 5 years from the diagnosis. The survival trend is increasing by period and decreasing creasing by age, both for men and women. The greatest gain in terms of survival was obtained by the elderly, with annual mean growth rates in the period 1978-1994 equal to 3.5% and 3.2% for men and women, respectively. More than 50% of the youngest cancer patients were “cured”, whereas for the elderly this proportion dropped to 15% and 25% for men and women, respectively. The South of Italy had the lowest survival and the North the most pronounced increase.

The obtained national survival estimates are similar, but not identical, to previously published estimates, in which Italian registries’ data were pooled without any adjustment for geographical representativeness. The four Italian areas have different survival levels and trends, showing variability within the country. The differences in survival between men and women may be explained by the different proportion of lethal cancers. Among males, most cases had a poor prognosis (lung and stomach cancers), whereas among females the largest proportion was made up of curable and less lethal cancers (breast cancer).

Sunburn during childhood is associated with an increased risk for developing melanoma in an adult age. The aim of the present study was to define the validity of our educational program in order to teach the positive effects and risks of sun exposure during childhood.

We conducted a population-based, case-control study in primary schools of three towns in Northern Italy (Brescia, Bergamo and Trento) between 2001 and 2002. The study was carried out on 1945 pupils (aged 8-9 years) and included 1309 case children who received an educational program before the summer to increase awareness towards sun exposure and 636 control children who did not. Parents of case and control children were interviewed using a questionnaire about their children's skin characteristics, sun protective behavior and sunburns. The questionnaire was completed twice, before and after the summer, to verify the changes of sun exposure habits.

A significant decrease in sunburns was demonstrated in the group of subjects who received the educational program, indicating the validity of our operative procedure (from 14.6% to 10%, P = 4 × 10⁻⁴).

Our educational melanoma program may be important to disseminate in a wider range of children a correct education on sun exposure during childhood.

Taxanes are largely metabolized and almost exclusively excreted in the feces by the liver through the biliary pathway, thus providing a rationale for investigating the activity of their hepatic artery delivery in case of liver metastases.

The aim of this study was to assess the feasibility of administering docetaxel via the hepatic artery in advanced breast cancer patients in whom the liver was the only or the predominant site of metastatic involvement. The dose was increased cycle by cycle in a prospective manner.

Ten eligible patients were enrolled. The median administered dose in the last cycle was 65 mg/m² (range, 40-100 mg/m²). The treatment was generally well tolerated, and only one patient stopped after two cycles because of toxicity. Four of the 9 eligible patients with assessable liver tumors achieved an objective response. After a median follow-up of 41 months, 4 of the 10 eligible (and 11 treated) patients were alive with a median overall survival of 46 months.

The administration of docetaxel via the hepatic artery is feasible. The highly interesting response and survival results observed in this limited series of patients warrant further studies.

A retrospective analysis was conducted to evaluate the tolerability as well as the impact of concurrent adjuvant CMF chemotherapy and radiation therapy on total CMF dose and dose intensity.

The medical records of 59 patients who had received conservative or radical surgery for breast cancer were analyzed. All patients had been assigned to 6 cycles of “1,8 CMF” adjuvant chemotherapy and concomitant radiation therapy. Total drug dose and dose intensity were calculated. Toxicity was recorded scored according to WHO criteria.

A total of 355 cycles was administered. Fifty of 59 patients received at least 85% of the programmed chemotherapy total dose, the median value being 100% (range, 42-100). The median relative dose intensity was 0.97 (range, 0.42-1.01). Forty-four of 59 (75%) patients experienced grade 3-4 neutropenia (20 febrile neutropenia) and 29 (49%) required G-CSF support.

This retrospective analysis showed that it is possible to give concurrent CMF and breast radiation while ensuring adequate chemotherapy total doses and dose intensities to most patients. However, G-CSF support is required in a significant proportion of patients.

Based on the results of previous phase I studies, in the current phase II trial we evaluated the efficacy and toxicity of cisplatin plus weekly docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC).

The eligibility criteria for the study included newly diagnosed stage IIIB/IV NSCLC, age ≤75 years, Eastern Cooperative Oncology Group performance status of 0-2, adequate organ functions, and signed informed consent. The chemotherapy regimen consisted of cisplatin, 80 mg/m² on day 1, and docetaxel, 25 mg/m² on days 1, 8 and 15 every 4 weeks.

Between January 2002 and December 2003, 31 patients with NSCLC were enrolled in the study. An objective response rate of 40% (95% CI, 21-60) was obtained in 27 assessable patients. The median time to progression was 6.4 months (range, 2.5-26.3) and median overall survival was 10.01 months (range, 5-28.3). The regimen was well tolerated with no grade 4 toxicity.

Cisplatin plus weekly docetaxel is an effective and well-tolerated regimen in chemo-naive patients with advanced NSCLC. A phase III study of weekly versus the conventional regimen of every three weeks should be conducted to compare the survival benefits, toxicity profile and quality of life.

In addition to bone marrow suppression and renal toxicity, neurotoxicity is a commonly occurring side effect of widely used chemotherapeutic agents like taxanes, cisplatin and vinca alkaloids. Neurotoxicity can cause antitumor therapy discontinuation or dose regimen modification. The aim of the present exploratory study was to investigate the activity of acetyl-L-carnitine in reversing peripheral neuropathy in patients with chemotherapy-induced peripheral neuropathy.

Twenty-seven patients (16 males and 11 females) with paclitaxel and/or cisplatin-induced neuropathy (according to WHO recommendations for the grading of acute and subacute toxic effects) were enrolled. Patients received at least one cisplatin- (n = 5) or one paclitaxel- (n = 11) based regimen, or a combination of both (n = 11). Patients with chemotherapy-induced peripheral neuropathy were treated with acetyl-L-carnitine 1 g/die iv infusion over 1-2 h for at least 10 days.

Twenty-six patients were evaluated for response having completed at least 10 days of acetyl-L-carnitine therapy (median, 14 days; range, 10-20). At least one WHO grade improvement in the peripheral neuropathy severity was shown in 73% of the patients. A case of insomnia related to ALC treatment was reported in one patient. Acetyl-L-carnitine seems to be an effective and well-tolerated agent for the treatment of chemotherapy-induced peripheral neuropathy.

Our preliminary results should be confirmed in double-blind, placebo controlled studies.

To correlate the treatment used in uterine sarcoma with outcome. The prognostic importance of pathology, clinical parameters and treatment are analyzed.

Forty patients (median age, 59 years; range, 37-85) with histologically verified uterine sarcoma were identified from a database compiled at the University of Florence from 1980 to 2001. Patients were followed for a median of 54 months (range, 3 months to 10 years). Twenty-four patients had leiomyosarcoma, 12 patients had mixed mullerian tumors, and 3 patients had endometrial stromal sarcoma. Stage I, II, III and IV tumors were identified in 22, 2, 9 and 7 patients, respectively. High, intermediate, low and unspecified grade sarcoma occurred in 9, 4, 5 and 22 patients, respectively.

At the time of analysis, 58% of patients had died and 42% were alive, with a median survival of 2 years from the initial diagnosis. Cause-specific survival for the entire group was 81%, 41% and 25% at 1, 3 and 5 years, respectively. In our series, univariate analysis for cause-specific survival did not demonstrate statistical significance for histology, grade, stage or age. There appeared to be a significant impact for postoperative radiotherapy in reducing local recurrence with a total dose higher than 50 Gy.

Our data favor treatment for uterine sarcoma with radical surgery plus irradiation, even in elderly patients.

To report clinical results in patients with testicular seminoma treated with postoperative radiotherapy with regard to survival, acute and late toxicity, and risk of second malignancy.

176 stage I-II testicular seminoma patients treated with radiotherapy from 1964 to 1994 at the Radiotherapy Division of Pisa University, using ⁶⁰Co or Linac, were analyzed retrospectively. The follow-up ranged from 0.13 to 32.37 years, with a median of 12.1 years. The observed numbers of second malignancies were compared with those expected, taking into account age, sex, and incidence rates from the Tuscany Tumor Registry.

Overall and specific survival at 10-15 years were 89-82% and 93-92%, respectively. Multivariate analysis revealed a significantly better survival in patients younger than 50 years and in those treated with Linac. Severe late sequelae occurred in 8% of the patients. Sixteen second malignancies were observed (14 solid tumors and 2 leukemias); median latency was 13 years (range, 3-27) and the observed/expected ratio 1.4 (P not significant). Solid cancers were localized in the bladder (2), kidney (2), skin (2), stomach (1), prostate (1), lung (1), larynx (1), uvea (1) and contralateral testicle (1); 1 patient presented an intestinal carcinoid and 1 a metastasis from an unknown primary. The risk of a second malignancy was higher in the patient group receiving less than 4000 cGy (observed/expected, 2.8; P = 0.015).

The study confirmed the high cure rate in stage III seminomas after postoperative radiotherapy. Incidence of a second malignancy was higher than expected, but the difference was not statistically significant.

We analyzed our own results in the treatment of male breast cancer patients with respect to local control, overall survival and possible prognostic factors for local and distant control.

Thirty-one patients with 32 carcinomas of the male breast were treated with radiotherapy. Twenty-five patients received radiotherapy to the chest wall including or not regional lymphatics after initial mastectomy (n = 23) or after surgery for local recurrence (n = 2). Median total dose was 60 Gy to the chest wall and 46 Gy to regional lymphatics. Seven patients with metastatic disease were referred for palliative radiotherapy.

Overall survival after postoperative radiotherapy was 40% after a median follow-up of 4.3 years. Actuarial 3-, 5- and 10-year survival was 82.6%, 56.5% and 43.5%, respectively. Five-year progression-free survival was 62.5%. Survival was significantly affected by the presence of lymph node metastases (P <0.001). Local recurrence was seen in one patient after 29 months.

Postoperative radiotherapy is important in the management of male breast cancer to improve local control and progression-free survival, resulting in one local failure in our analysis. The presence of lymph node metastases significantly impairs survival.

The National Working Group on Prostate Radiotherapy of AIRO (Associazione Italiana Radioterapia Oncologica, Italian Association of Radiotherapeutic Oncology) was established in March 2001. A retrospective multicenter survey was performed to analyze the patterns of care for prostate cancer patients treated with postoperative radiotherapy following radical prostatectomy in Italy with regard to the year 2000.

A structured questionnaire was mailed to 47 Italian radiotherapy centers to assess patient accrual in the postoperative setting in the interval comprised between period January-December 2000. Numbers of patients treated for different stages, specific prognostic factors indicating the need for adjuvant radiotherapy, fractionation schedules and prescription doses were acquired as well as other clinically important factors such as radiotherapy timing and the use of hormone therapy. More technical features of the treatment, such as patient positioning, mode of simulation, typical field setup and dose prescription criteria were also included in the questionnaire.

The questionnaire was returned by 24 radiotherapy Institutions (51%) with a total number of 470 patients treated postoperatively in the year 2000. An average of about 20 patients were enrolled by each radiotherapy center. The age range was 45-81 years. Radiotherapy was delivered within 6 months of radical prostatectomy in 297 patients (65.4%) (mean, 3.4 months). In 157 (34.6%), the treatment was delivered as a salvage approach for biochemical or micro-macroscopic recurrence. Most of patients had locally advanced stage disease (pT3-pT4) (76%). Unfavorable prognostic factors, such as positive margins, capsular invasion, Gleason pattern score <7 were present in about 50% of patients.

The study confirmed that important risk factors for recurrences are present in a significant percentage of patients treated by radical prostatectomy. The number of patients that would benefit from adjuvant radiotherapy is therefore potentially very large. Future prospective studies should be conducted to assess and to clarify the respective roles of adjuvant and salvage radiotherapy in prostate cancer patients.

Carcinoma of the colon-rectum is an infrequent cause of brain metastases, constituting 1-5% of all metastatic lesions to the brain. We reviewed our experience in the treatment of brain metastases from colorectal cancer to define the efficacy of whole brain radiation therapy as a palliative measure in this setting of patients.

Twenty-three consecutive cases of brain metastasis from colorectal cancer treated between 1999 and 2004 were identified in the files of the Division of Radiotherapy of the A Businco Regional Oncological Hospital, Cagliari. Their records were reviewed for patient and tumor characteristics and categorized according to the RTOG RPA classes.

Fifteen patients (65%) had multiple metastases. Twenty-one patients (91%) showed extracranial metastases. Fourteen patients were classified as RTOG RPA class II and 9 class III. The median radiation dose delivered was 2000 cGy in 5 fractions in one week (range, 20-36 Gy). In 14 of 20 assessable patients (70%), symptomatic improvement was observed. The median follow-up and survival time for all the patients, 12 females and 11 males, was 3 months. In 3 patients only the cause of death was the brain metastasis.

Despite the disappointing survival time, external radiation therapy to the whole brain proved to be an efficacious palliative treatment for patients with multiple or inoperable brain metastasis from colorectal cancer.

Regional lymph node (LN) involvement in colorectal cancer (CRC) identifies the stage and the subset of patients who would benefit from adjuvant chemotherapy. We performed a retrospective analysis to determine if the number of recovered LNs was associated with long-term outcome in patients operated on for stage II and III CRC.

Hospital records of 179 patients with CRC followed in our unit from 1997 to April 2003 were reviewed.

On average 11.68 ± 7.3 LNs were sampled per surgical specimen. Sampling of at least nine LNs appeared to be the minimum number required for accurately predicting LN involvement (P = 0.002). Three-year rates of disease-free survival (DFS), local recurrence-free survival (LRFS) and overall survival (OS) were lower in patients with fewer than nine LNs sampled (P = 0.032, P = 0.006 and P = 0.04, respectively). However, this had no impact on the three-year distant metastasis-free survival rate (DMFS) (P = 0.472). In stage II disease, patients with nine or more LNs dissected had significantly higher three year DFS and LRFS rates than the subgroup with fewer than nine LNs dissected (P = 0.024 and P = 0.015, respectively), but this did not have any effect on DMFS or OS (P = 0.406 and P = 0.353, respectively).

Current protocols provide adjuvant treatment in stage III patients; the problem is to correctly determine stage by recovering as many LNs as possible.

The aim of this study was to assess whether intraoperative radiolocalization of head and neck paragangliomas with ¹¹¹In-pentetreotide may increase surgical effectiveness, reducing the risk of recurrence.

Our study included eight patients with untreated, recently diagnosed paragangliomas (four unilateral and four bilateral tumors of the carotid body). After iv injection of −150 MBq ¹¹¹In-pentetreotide, preoperative somatostatin receptor scintigraphy (SRS) was performed. SPECT of the neck was performed at four hours and planar Images of the head and neck were also obtained at four and 24 hours post injection. Scintigraphy was always compared with the results of conventional imaging methods (MRI, angiography and sonography). Intraoperative detection was performed on 11 lesions 24 hours after radiopharmaceutical administration using a handheld gamma probe.

Preoperative SRS showed high radiotracer uptake in all patients. All the intraoperatively detected lesions were radically resected and histologically confirmed to be involved by tumor. No false positive results were recorded. Gamma probe detection revealed a small intracranial extension not detected by other imaging methods in a patient with a paraganglioma of the right carotid, and partial involvement of the carotid artery in another patient. During follow-up (median 3.5 years; range, 4 months-7 years) all patients remained disease free according to all parameters.

To our knowledge, this is the first experience of radioguided surgery in paraganglioma. Although our study included a relatively small number of patients, we suggest that intraoperative gamma probe detection may be a powerful tool to improve surgical effectiveness.

This study was aimed at analyzing metastatic involvement in interpectoral (Rotter's) lymph nodes in relation to tumor location, size, grade and hormone receptor status in primary breast cancer.

The study included 172 female patients undergoing surgery for breast cancer at the University Hospital for Tumors, Zagreb, Croatia from November 2001 to August 2003. In addition to the standard surgical procedure, interpectoral (Rotter's) lymph nodes were removed in all of the patients. Serum levels of the tumor marker CA 15-3 were determined before surgery and hormone receptor status after surgery.

Rotter's lymph nodes were identified in 67% of the patients, with metastatic involvement being found in 20% of the Rotter's nodes. Metastatic involvement of Rotter's nodes in patients with negative and positive axillary lymph nodes was 4% and 35%, respectively. When we looked at the location of the tumor in patients with metastatic involvement of Rotter's nodes, we found that tumors located in the upper quadrants were more prone to metastasis to Rotter's nodes; there was a significant positive correlation between tumor location and positive Rotter's nodes (r = 0.953, P = 0.012). As regards tumor size, Rotter's nodes were identified in 15%, 20% and 30% of stage T1 (<2 cm), T2 (2-5 cm) and T3 (>5 cm) tumors, respectively. Hormone receptor status showed no statistically significant difference in the expression of estrogen and progesterone receptors between patients with and those without positive Rotter's nodes. Of 35 Rotter's node-positive patients, 31.4% had elevated serum levels of CA 15-3; the level was significantly higher in Rotter's-positive patients compared to those with negative (or absent) Rotter's nodes.

The results show that one-fifth of breast cancer patients, or even one-third of those with positive axillary lymph nodes, are discharged with positive interpectoral lymph nodes that remain undiagnosed. As the nodes can be surgically removed without additional mutilation, exploration of Rotter's lymph nodes should be introduced into routine clinical practice.

In this study we aimed to determine the prognostic factors affecting local control (LC) in limited glottic carcinoma treated with definitive radiotherapy (RT).

Between June 1991 and December 2001, 114 patients with early squamous-cell carcinoma of the glottis were treated with definitive RT at our institution. Only four (3.5%) patients were women. The median age was 60 (27-79). Fifteen percent, 72% and 13% of the patients had Tis, T1 and T2 tumors, respectively. Forty-three (37.7%) patients had anterior commissure invasion. Prior to RT 35 (31%) patients had undergone vocal cord stripping and two (2%) cordectomy. A median dose of 66 Gy (50-70.2) was given over a median period of 46 days (20-60). Univariate and multivariate analyses were performed for LC. The prognostic parameters analyzed for LC were T classification, anterior commissure involvement, total RT dose, and overall treatment time.

Five-year local and regional control rates were 84.2% and 97.7%. RTOG grade 3-4 late side effects were observed only in one (0.9%) patient. In 15 patients with local failure, salvage treatment consisted of partial laryngectomy in eight patients and total laryngectomy in five. One of the remaining two patients was medically inoperable, and the other refused salvage surgery. In one of the three patients with regional failure, salvage surgery was applied and the other two were given palliative chemotherapy because of unresectable disease. Following salvage treatments, the ultimate five-year LC rate was 96.9% and the five-year larynx preservation rate was 91.1%. Second primary cancer was diagnosed in 17 (14.9%) patients. Only one patient developed distant metastases and two patients died of laryngeal cancer. While T2 disease and anterior commissure involvement were found to be unfavorable prognostic factors significantly influencing LC in univariate analyses, only T2 disease remained independent in multivariate analysis.

In patients with early glottic carcinoma, T classification proved to be the only independent prognostic factor affecting LC after primary radiotherapy according to the results of this study.

The purpose of this study was to assess the association between highly-oncogenic types HPV DNA detection by Hybrid Capture II (HCII) and residual or recurrent high-grade cervical intraepithelial neoplasia (CIN 2 or 3) during the follow-up of women submitted to large loop excision of the transformation zone (LLETZ).

In this cohort study, 94 women submitted to LLETZ because of CIN 2 or 3 between March 2001 and September 2002 were followed up twice yearly until September 2003. Follow-up visits consisted of an interview regarding clinical, social and demographic characteristics complemented with gynecological examination with specimen collection for Pap test and HCII and colposcopy. Eighty-one patients attended the first visit (mean 4.8 months, range 3-6) and 75 the second visit (mean 10.9 months, range 7-17 months). McNemar's test to assess the variation of HPV DNA detection following LLETZ, odds ratios (OR) to evaluate the correlation between HPV DNA positivity and residual/recurrent CIN during follow-up, and logistic regression to assess the risk of residual/recurrent CIN were used.

There was a strong and significant reduction in HPV detection after LLETZ (P <0.001). HPV DNA detection was correlated with residual/recurrent CIN at the first (OR = 103.4; 95% CI 5.5 to 1961.2) and second (OR = 12.7; 95% CI 1.1 to 345.5) follow-up visits. Multivariate analysis showed HPV persistence as a stand-alone risk factor for residual/recurrent CIN (OR = 50.3; 95% CI 3.8 to 663.1).

High risk HPV DNA detection decreased substantially after CIN treatment with LLETZ, but HPV persistence was strongly correlated with residual/recurrent CIN.