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The role of temozolomide concurrent with and adjuvant to radiotherapy (RT/TMZ) in elderly patients with glioblastoma (GBM) remains unclear. We evaluated the outcome of patients >70 years in the context of the Project of Emilia-Romagna Region in Neuro-Oncology (PERNO), the first Italian prospective observational population-based study in neuro-oncology. For this analysis the criteria for selecting patients enrolled in the PERNO study were: age >70 years; PS 0–3; histologically confirmed GBM; postoperative radiotherapy (RT) after surgery with or without concomitant temozolomide (TMZ) or postsurgical TMZ alone. Between January 2009 and December 2010, 76 GBM elderly patients were identified in the prospective PERNO study. Twenty-three patients did not receive any treatment after surgery, and 53 patients received postsurgical treatments (25 patients received RT alone and 28 patients RT/TMZ). Median survival was 11.1 months (95 % CI 8.8–13.5), adding temozolomide concomitant and adjuvant to radiotherapy it was 11.6 months (95 % CI 8.6–14.6), and 9.3 months (95 % CI 8.1–10.6) in patients treated with RT alone (P = 0.164). However, patients with MGMT methylated treated with RT/TMZ obtained a better survival (17.2 months, 95 % CI 11.5–22.9) (P = 0.042). No difference in terms of survival were observed if patients with MGMT unmethylated tumor received RT alone, or RT/TMZ or, in MGMT methylated tumor, if patients received radiotherapy alone. In elderly patients RT/TMZ represent a widely used approach but it is effective with methylated MGMT tumors only.

Purpose: To verify the feasibility of, and quantify the risk of, pneumonitis from locoregional radiotherapy (RT) after high-dose dense chemotherapy with epirubicin and paclitaxel with peripheral blood progenitor cell support in patients with high-risk Stage II-III breast cancer. Methods and Materials: Treatment consisted of a mobilizing course of epirubicin 150 mg/m 2 , preceded by dexrazoxane (Day 1), paclitaxel 175 mg/m 2 (Day 2), and filgrastim; followed by three courses of epirubicin 150 mg/m 2 , preceded by dexrazoxane (Day 1), paclitaxel 400 mg/m 2 (Day 2), and peripheral blood progenitor cell support and filgrastim, every 16–19 days. After chemotherapy, patients were treated with locoregional RT, which included the whole breast or the chest wall, axilla, and supraclavicular area. Results: Overall, 64 of 69 patients were evaluable. The interval between the end of chemotherapy and the initiation of RT was at least 1.5–2 months (mean 2). No treatment-related death was reported. After a median follow-up of 27 months from RT (range 5–77 months), neither clinically relevant radiation pneumonitis nor congestive heart failure had been reported. Minor and transitory lung and cardiac toxicities were observed. Conclusion: Sequential high doses of epirubicin, preceded by dexrazoxane, and paclitaxel did not adversely affect the tolerability of locoregional RT in breast cancer patients. The risk of pneumonitis was not affected by the use of sequential paclitaxel with an interval of at least 1.5–2 months between the end of chemotherapy and the initiation of RT. Long-term follow-up is needed to define the risk of cardiotoxicity in these patients.

Continuing medical education (CME) has always been considered very important in modern medical practice. Physicians should not be left completly free to continuously educate themselves, but they should receive at least a minimal level of education accreditated by scientific and/or Government Institutions. The main goal of CME is to improve the quality of medical practice. In order to adequately define programs and contents of CME in radiation oncology, we must first identify the professional profile of the radiation oncologist: he is a physician engaged in the clinical practice of oncology, and in particular in the loco-regional cure of cancer by sophisticated technologies; he has the responsibility of diagnosis, treatment, follow-up and supportive care of cancer patients, collaborating within a multidisciplinary approach with the radiologist, the medical oncologist, the surgeon and the medical physicist. The european core curriculum in radiotherapy and the procedures employed in the daily practice could be models to develop postgraduate teaching and CME for the radiation oncologists in Italy. In fact, many countries, such as the USA, France, Belgium and the United Kingdom, have already developed accreditated programs of CME. Unfortunately, Italy still lacks this type of program. What is mostly needed to implement CME activities is a close cooperation between representatives of radiation oncology associations and Government Institutions to define laws, programs, an Accreditation Council, a minimum of formative credits, accreditated categories of education regulating CME, as well as the resources devoted to it.

Several biomarkers have been proposed as useful parameters to better specify the prognosis or to delineate new target therapy strategies for glioblastoma patients. MicroRNAs could represent putative target molecules, considering their role in tumorigenesis, cancer progression and their specific tissue expression. Although several studies have tried to identify microRNA signature for glioblastoma, a microRNA profile is still far from being well-defined. In this work the expression of 19 microRNAs (miR-7, miR-9, miR-9∗, miR-10a, miR-10b, miR-17, miR-20a, miR-21, miR-26a, miR-27a, miR-31, miR-34a, miR-101, miR-137, miR-182, miR-221, miR-222, miR-330, miR-519d) was evaluated in sixty formalin-fixed and paraffin-embedded glioblastoma samples using a locked nucleic acid real-time PCR. Moreover, a comparison of miRNA expressions was performed between primary brain neoplasias of different grades (grades IV-I). The analysis of 14 validated miRNA expression in the 60 glioblastomas, using three different non-neoplastic references as controls, revealed a putative miRNA signature: mir-10b and miR-21 were up-regulated, while miR-7, miR-31, miR-101, miR-137, miR-222 and miR-330 were down-regulated in glioblastomas. Comparing miRNA expression between glioblastoma group and gliomas of grades I-III, 3 miRNAs (miR-10b, mir-34a and miR-101) showed different regulation statuses between high-grade and low-grade tumors. miR-10b was up-regulated in high grade and significantly down-regulated in low-grade gliomas, suggesting that could be a candidate for a GBM target therapy. This study provides further data for the identification of a miRNA profile for glioblastoma and suggests that different-grade neoplasia could be characterized by different expression of specific miRNAs.

Glioblastoma is the most aggressive brain tumor that may occur in adults. Regardless of the huge improvements in surgery and molecular therapy, the outcome of neoplasia remains poor. MicroRNAs are small molecules involved in several cellular processes, and their expression is altered in the vast majority of tumors. Several studies reported the expression of different miRNAs in glioblastoma, but one of the most critical point in understanding glioblastoma miRNAs profile is the comparison of these studies. In this paper, we focused our attention on the non-neoplastic references used for determining miRNAs expression. The aim of this study was to investigate if using three different non-neoplastic brain references (normal adjacent the tumor, commercial total RNA, and epileptic specimens) could provide discrepant results. The analysis of 19 miRNAs was performed using Real-Time PCR, starting from the set of samples described above and the expression values compared. Moreover, the three different normal RNAs were used to determine the miRNAs profile in 30 glioblastomas. The data showed that different non-neoplastic controls could lead to different results and emphasize the importance of comparing miRNAs profiles obtained using the same experimental condition.

Background Neoadjuvant chemoradiotherapy is the treatment of choice in advanced rectal cancer, even though there are many patients who will not benefit from it. There are still no effective methods for predicting which patients will respond or not. The present study aimed to define the genomic profile of rectal tumors and to identify alterations that are predictive of response in order to optimize therapeutic strategies. Methods Forty-eight candidates for neoadjuvant chemoradiotherapy were recruited and their pretherapy biopsies analyzed by array Comparative Genomic Hybridization (aCGH). Pathologic response was evaluated by tumor regression grade. Results Both Hidden Markov Model and Smoothing approaches identified similar alterations, with a prevalence of DNA gains. Non responsive patients had a different alteration profile from responsive ones, with a higher number of genome changes mainly located on 2q21, 3q29, 7p22-21, 7q21, 7q36, 8q23-24, 10p14-13, 13q12, 13q31-34, 16p13, 17p13-12 and 18q23 chromosomal regions. Conclusions This exploratory study suggests that an in depth characterization of chromosomal alterations by aCGH would provide useful predictive information on response to neoadjuvant chemoradiotherapy and could help to optimize therapy in rectal cancer patients. The data discussed in this study are available on the NCBI Gene Expression Omnibus [GEO: GSE25885].

From June 1991 to August 1994, 61 patients with stage III unresectable non-small-cell lung cancer (NSCLC; 16 cases of stage IIIA with N2 bulky disease and 45 cases of stage IIIB) were treated with ifosfamide given i.v. at 3 g/m2 on day 1, carboplatin given i.v. at 200 mg/m2 on days 1 and 2, etoposide given i.v. at 120 mg/m2 on days 1-3 (ICE) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) given s.c. at 5 micrograms/kg on days 4-13. Chemotherapy was given every 3 weeks for up to three cycles and, unless the disease progressed, was followed by thoracic radiotherapy on the tumor volume (total dose 60 Gy) and mediastinum (40 Gy). All patients had measurable or evaluable unresectable disease and a performance status (Eastern Cooperative Oncology Group) of 0-1. Only 61% of the enrolled patients received the full program of chemoradiotherapy according to the study design. At the end of sequential chemo-radiotherapeutic treatment, 41% of the patients had an objective response (24 partial responses and 1 complete response), 31% showed no change and 28% had progressive disease. The response rate noted for patients in stage IIIA with N2 bulky disease and that recorded for patients in stage IIIB did not differ significantly. The median time to progression was 5.4 months and the median survival was 8.2 months, with the 1-year survival rate being 31%. Sites of progression were mostly intrathoracic. Haematological toxicity was the main side effect, with grade III-IV thrombocytopenia being reported in 24% of the 165 courses of intensive ICE chemotherapy given. Febrile neutropenia was described in six courses (three patients). Non-haematological toxicities and radiotherapy-related side effects were generally mild and easily manageable. In conclusion, in unresectable stage III NSCLC a short program of moderately intensified ICE chemotherapy with rhG-CSF protection followed by sequential radiotherapy failed to increase the percentage of objective responses and reached a median survival comparable with that previously achieved with standard doses.

Aims and Background After radical cystectomy, with or without pelvic radiotherapy, more than 50 % of patients affected by infiltrating bladder cancer died of distant metastases. Polychemotherapy yields 25 % complete remissions (CR) in patients with invasive transitional cell bladder carcinoma; although many concerns exist about the duration of such CR. This study was undertaken with the aim of evaluating the efficacy and safety of an integrated chemo-radio-therapeutic treatment, in order to broaden indications to a conservative surgical therapy. Methods Thirty-three consecutive patients with bladder urothelial cancer T2-T4, N0, M0, have been treated. Patients received neoadjuvant chemotherapy (rescue-M-VEC) consisted of methotrexate 30 mg/sqm plus folinic acid 15 mg after 24 h on days 1, 15, 22; vinblastine 3 mg/sqm on days 1, 15 and 22; epidoxorubicin 30 mg/sqm on day 1; cisplatin 70 mg/sqm on day 1. This cycle was repeated on day 29. After 2 cycles of rescue-M-VEC, patients underwent pelvic cobalt teletherapy 40 Gy combined with low dose cisplatin 25 mg/sqm/week. After restaging, responding patients underwent further radiation therapy (24 Gy) as booster consolidation. Results After 2 cycles of chemotherapy and pelvic radiotherapy 14/31 evaluable patients (45.2 %) achieved CR and 11/31 (35.4 %) partial remission, with an overall response rate of 80.6 % (25/31). With a median follow up of 21 months the actuarial survival rate at 24 months was equal to 79.8 %. Eleven radical cystectomies were performed, 6 of which at restaging in non responding patients and 5 during the follow up due to relapse. Of the 25 patients selected for bladder conservation, 12 (48 %) have not yet shown relapses. Three out of 31 (9.7 %) patients died of distant metastases. No severe toxicity has been observed: moreover no patient developed stomatitis after chemotherapy. Conclusions Our results seem encouraging but longer follow-up and further phase III studies need to be carried out to demonstrate the feasibility of conservative treatment in muscle infiltrating bladder cancer.

We assessed the outcome in 65 patients with limited small cell lung cancer (SCLC) treated from 1980 through 1989 with combination chemotherapy and chest and cranial irradiation. Of the 65 patients, 32.3 % (21/65) achieved a complete remission (CR) prior to radiation therapy; six additional cases achieved a CR after radiotherapy with an improvement of 10% in the incidence of CR. In our group, 8 patients were alive and free of disease at 30 months (12.3 %). We think that a combination of local thoracic irradiation in SCLC limited disease plus chemotherapy yields more CR and improves survival, especially in the group of patients who obtained the CR after initial induction chemotherapy.

From 1979 to 1986, 182 patients with biopsy proven diagnosis of Ewing's sarcoma of bone were observed. One hundred of the 182 patients (72 males, 28 females, median age 15.8 years) with localized disease and no previous treatment were treated with chemotherapy (VCR, ADM, CTX, D-ACT) for 15-18 months. Local treatment was radiotherapy (42 patients), surgery (31 patients), or a combination of both (27 pts). Radiation doses ranged from 45 to 64 Gy given with conventional fractionation. Median follow-up was 51.2 months (24-106). Overall and disease-free survival were, respectively, 58.7 and 42.6%. Resected patients tended to have a better local control (Surgery 93.6%, Surgery + Radiation therapy 92.6%, Radiation therapy 69.1%). Disease-free survival was significantly related to the volume of the primary tumor (bulky: 33.2%, not-bulky: 57.7%), to site (extremities 54.6%, central sites 16.6%, other sites 40.9%), and to local treatment (Radiation therapy 30.3%, Surgery + Radiation therapy 47.9%, Surgery 59.1%). These results are, however, biased because resected patients tended to have smaller tumors in favorable sites.

The authors report on the results obtained in 30 consecutive cases of primary non-Hodgkin's lymphoma of bone (PNHLB) treated at the Istituto Ortopedico Rizzoli between 1972 and 1982. Four patients were treated with radiotherapy only and 26 were treated with radiotherapy plus adjuvant chemotherapy. At a median follow-up of 86 months (range, 30–160), among the 26 patients treated with chemotherapy also there were 3 relapses (2 had meningeal involvement and 1 had recurrence in another bone). Relapse (local recurrence plus multiple new localizations) was observed in one of the four patients treated with radiotherapy only. These results are compared with the results of 68 patients with Ewing's sarcoma who were treated during the same period with radiation therapy and adjuvant chemotherapy and reported in a previous study. In this group, the disease-free survival rate was only 32% (20/68) with a much higher incidence of local recurrence (31%). The necessity of making a clear distinction between PNHLB and Ewing's sarcoma is discussed. Cancer 57:1468–1472, 1986.

Between February 1982 and June 1984, 36 previously untreated patients with high-grade non-Hodgkin's lymphomas (NHL) according to the Kiel classification were treated with an intensive therapeutic regimen including cyclophosphamide, vincristine, doxorubicin, prednisone, cytarabin, VM 26 and local radiotherapy on bulky disease. Twenty-three patients (64 %) achieved a complete remission and 11 patients (30 %) had a partial response. Over a median follow-up from the diagnosis of 32.5 months, the overall survival was 55 %; relapse-free survival for complete responders was 56.5 %. Toxicity was irrelevant. This regimen was effective in the treatment of high-grade NHL, but probably needs intensification and rotation of different drugs.

Thirty consecutive cases of localized primary non-Hodgkin's lymphoma of bone (PNHLB) were treated in a 10-year period at the Istituto Ortopedico Rizzoli with localized radiation (4 cases) and localized radiation and adjuvant chemotherapy (26 cases). The doses of radiation varied from 3000-4500 rad. A variety of staging procedures evolving with new diagnostic techniques over the 10 years were performed. Adjuvant chemotherapy comprised two different regimens of vincristine, adriamycin and cyclophosphamide. Twenty-four of the 26 patients (92 %) have been free of disease with a median follow-up of 75.5 months (18-144 months). Two patients developed meningeal involvement and one patient, treated with radiation therapy only, developed a local recurrence. The results are compared to the management of 68 Ewing's sarcoma patients treated during the same period. Here, higher doses of localized radiation therapy (approximately 5000 rad) and similar adjuvant chemotherapy were administered. The survival was 32 % (22/68) with a higher incidence of local recurrence (21 %). These data indicate that PNHLB should be considered a separate entity from Ewing's sarcoma and can be treated successfully with lower doses of radiation to the primary tumor and adjuvant chemotherapy. The observations are also compared to a variety of other biological characteristics of Ewing's sarcoma. Since only two patients developed meningeal relapse, our experience does not permit a firm recommendation for routine prophylactic treatment of the central nervous system in PNHLB.

Primary gastric lymphoma accounts for about 2% of gastric neoplasms. The prognosis of patients affected with non-Hodgkin's gastric lymphoma appears better than for other lymphatic sites. In a retrospective study, the authors have analyzed 45 patients, by evaluating the histopathologic characteristics and relative prognostic factors. The main factors significantly influencing 5-yr survival are: serosal penetration (31.17% vs. 71.2%, P less than 0.05), regional lymph node involvement (53.07% vs. 68%), and clinical stage of disease (IE: 85.6%, IVE:10%, P less than 0.001). The histologic characteristics, the high or low grade of malignancy, and patient age can also be considered important prognostic factors, but not statistically significant in our series of cases. Comparison between overall survival and disease-free survival of patients in stages IE and IIE who underwent surgery alone, with those who had chemotherapy and/or radiotherapy after surgery shows a higher survival (85.6%) of the group who had combined treatments, even though this difference is not statistically significant.

Five hundred and seven patients with Hodgkin's lymphoma (HL), forming the basis of our 18 years experience, are retrospectively analyzed. Four therapeutic periods are recognizable: The 1966-1970 period was characterized by the absence of treatment and management policy. The 55 patients entered in this period experienced 70 and 56% survival at 5 and 10 yr, respectively, from diagnosis. The 1971-1974 period was characterized by the increasing knowledge of staging relevance and therapeutic approaches. The 153 patients who were treated in this period experienced 72 and 60% survival at 5 and 10 yr, respectively. The 1975-1980 period was characterized by a large combination of MOPP and radiotherapy. The 216 patients who entered this period observed 80 and 72.5% survival at 5 and 10 yr, respectively. The last therapeutic period (1980 to present time) is characterized by the increasing relevance of prognostic factors and alternating use of MOPP and ABVD as non-cross resistant regimen. The 83 patients who entered this period showed 90% survival at 5 yr. Both survival and disease-free survival were positively influenced by the change of therapeutic strategies during the four periods (P less than 0.005). Although better results have been recorded moving from one to the next therapeutic period, the present policy has been also based on the recognition of a high number of late complications due to the therapy. Preliminary results about the present therapeutic experience seem to indicate both a good remission rate and low incidence of complications.

Ninety-six patients with pathological stage IIIs Hodgkin's disease, uniformly treated with six cycles of MOPP and TNI, were retrospectively analysed in an effort to determine whether the lymphographic aspect of lymph nodes influence the prognosis. Case material was grouped according to the presence of lymph nodes less than 3 cm in diameter or larger at lymphography. Five-year survival and disease-free survival were 85 and 78% for patients with small lymph node involvement, compared to 48 and 30% for patients with larger lymph nodes. The comparative analysis between the lymphographic aspect and other prognostic factors shows that large lymphographic involvement is strongly correlated with the presence of large spleen involvement (P less than 0.0000029), followed by stage III2 (P less than 0.000612), followed by greater than or equal to 5 involved sites (P less than 0.012), followed by age greater than 40 yr (P less than 0.047). Conversely, no significant correlation was found with symptoms, histology and mediastinal involvement. Modifications of current treatment for both large and small lymph node involvement are discussed.

Summary From 1976 to 1982, 78 patients with nasopharyngeal cancer (NPC) were treated with definitive megavoltage irradiation in accordance with a uniform protocol. The results of treatment were analyzed and prognostic factors reviewed. The incidence of primary failures was directly related to the extent of nasopharyngeal disease, since the relapse rate was 11% in T1T2 patients compared with 37.5% in T3T4 patients. Similarly, failure in the neck correlated with the N stage, being negligible for N0 and N1, while 35.7% for N3. The presence of bulky cervical nodes was associated with a higher risk for metastases: hematogenous dissemination occurred in 50% of N3B patients. The histology pattern seemed to significantly affect the ultimate outcome of patients with NPC, since disease-free survival was 65.5% in patients with a diagnosis of undifferentiated carcinoma (UC) and 23.8% in patients with squamous cell carcinoma (SC). The major cause of poor survival in this latter patient group was not only a higher recurrence rate of both primary and nodal disease but a greater incidence of distant metastases as well.

The results of 144 previously untreated cases of primary Ewing's sarcoma of bone are reported with a minimum follow-up of 5 years. This series was treated between 1972 and 1982 at Istituto Ortopedico Rizzoli with a combined therapy. The local control of the disease consisted of amputation (ten cases), resection followed by radiation therapy (35-45 Gy) (48 cases) and radiation therapy alone (40-60 Gy) (86 cases). Adjuvant chemotherapy, rigorously standardized, was performed according two different protocols: the first (85 cases treated in the period 1972-1978) consisted of vincristine (VCR) Adriamycin (doxorubicin) (ADM), and cyclophosphamide (EDX); the second (59 cases treated in the period 1979-1982) of VCR, ADM, EDX and dactinomycin (DACT). At a follow-up of 5 to 16 years (median, 9), 59 patients (41%) are continuously disease-free (CDF), 81 (56%) developed metastatic disease and/or local recurrence, and four (3%) had a second malignancy. Three factors seem to be correlated to prognosis: the site of the initial lesion (only 23% of the pelvic lesions are represented in the CDF group versus 46% of the other locations); the chemotherapy protocol (32% of the cases in the first protocol are CDF versus 54% in the second); the type of local treatment (60% of the patients treated with amputation or resection plus radiotherapy versus 28% of those treated with radiation therapy alone are CDF). A local recurrence was observed in 24% of the patients (8% in the group locally treated with surgery or surgery plus radiation therapy versus 36% in the group treated with radiation therapy alone). These data suggest that even though adjuvant chemotherapy can improve the long-term results in localized Ewing's sarcoma patients, this disease still represents, in a high percentage of cases, a lethal process whose final prognosis widely depends on the local control of the lesion. Due to the questionable effect of the radiation therapy alone in controlling the primary lesion and its important side effects, the role of surgery in treating Ewing's sarcoma of bone should be extended.

Background As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. Methods Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. Results Two hundred sixty-seven GBM patients (median age, 64 y; range, 29–84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2–12.4). The 139 patients ≤aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0–18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248–0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388–0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328–0.986; P = .0446). Conclusions The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged ≤70 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor.

Germ cell tumors are rare neoplasms that affect young males. Nearly 99% of patients with localized stage I disease and nearly 80% of patients with metastatic disease can be cured. Even patients who relapse following chemotherapy can achieve a long-term survival in approximately 30–40% of cases. The main objective in early stages and in good prognosis patients has changed in recent years, and it has become of major importance to reduce treatment-related morbidity without compromising the excellent long-term survival rate. In poor prognosis patients, there is a correlation between the experience of the treating institution and the long-term clinical outcome of the patients, particularly when the most sophisticated therapies are needed. So far, of utmost importance is the information from updated practice guidelines for the diagnosis and treatment of germ cell tumors. The Italian Germ cell cancer Group (IGG) has developed the following clinical recommendations, which identify the current standards in diagnosis and treatment of germ cell tumors in adult males.