Nasopharyngeal carcinoma in a low incidence European area : A prospective observational analysis from the Head and Neck Study Group of the Italian Society of Radiation Oncology (AIRO).

PURPOSE: To evaluate the outcomes with respect to long-term survival and toxicity in patients with nasopharyngeal carcinoma (NPC) treated in a European country with low incidence. MATERIALS AND METHODS: A prospective observational study carried out by the AIRO Head and Neck group in 12 Italian institutions included 136 consecutive patients treated with radiotherapy (RT) ± chemotherapy (CHT) for NPC (without distant metastasis) between January 1, 2008 and December 31, 2010. RESULTS: The disease-specific survival (DSS), overall survival (OS), and disease-free survival (DFS) at 5 years were 92 (±2), 91 (±3), and 69 % (±5 %), respectively. Distant failure was the most frequent modality of relapse. The local, regional, and locoregional control at 5 years were 89 (±3), 93 (±3), and 84 % (±4 %), respectively. The incidence of acute and late toxicity and the correlations with different clinical/technical variables were analyzed. Neoadjuvant CHT prolongs radiotherapy overall treatment time (OTT) and decreases treatment adherence during concomitant chemoradiotherapy. An adequate minimum dose coverage to PTV(T) is a predictive variable well related to outcome. CONCLUSION: Our data do not substantially differ in terms of survival and toxicity outcomes from those reported in larger series of patients treated in countries with higher incidences of NPC. The T stage (TNM 2002 UICC classification) is predictive of DSS and OS. The GTV volume (T ± N) and an adequate minimum PTV(T) coverage dose (D95 %) were also identified as potential predictive variables. Sophisticated technologies of dose delivery (IMRT) with image-guided radiotherapy could help to obtain better minimum PTV(T) coverage dose with increased DFS; distant metastasis after treatment still remains an unresolved issue.

Parameters and outcomes in 525 patients operated on for oral squamous cell carcinoma.

PURPOSE: This report analyzed the outcomes of patients undergoing surgery for oral squamous cell carcinoma (OSCC) to identify the value of prognostic factors. MATERIAL AND METHODS: A total of 525 patients were studied who had undergone surgery for oral squamous cell carcinoma (OSCC) between 2000 and 2011, of whom 222 had received postoperative radiation-therapy (PORT) and or chemoradiation-therapy (PORTC). For each patient, personal data, histological findings, treatment and outcome were recorded and analyzed statistically. Survival curves were calculated using the Kaplan-Meier algorithm, and the difference in survival among subgroups was examined. RESULTS: The overall survival (OS) and disease-specific survival (DSS) 5-year survival rate in the 525 patients were respectively 71.38% and 73.18%. The differences in the overall survival and disease-specific 5-year survival were significant (p < 0.05) for age < 40 years, site of origin, N status, staging, grading, osseous medullar infiltration, and perineural invasion. In patients undergoing radiation therapy, only perineural invasion negatively influenced the survival prognosis. In 150 pT1 cases of tongue and floor-of-mouth cancer, an infiltration depth (ID) > 4 mm was statistically correlated with poorer prognosis. CONCLUSIONS: The results demonstrate an improvement in the 5-year OS and DSS rates during the past decade compared with the previous decade. Univariate analysis revealed that age, tumor staging, and lymph node involvement, extracapsular spread, grading, perineurial invasion, infiltration depth, and osseus medullary invasion were associated significantly with overall survival and disease-specific survival.

Efficacy and feasibility of induction chemotherapy and radiotherapy plus cetuximab in head and neck cancer.

BACKGROUND: To determine the potential activity and tolerability of sequential treatment in head and neck cancer, we conducted a phase II trial based on induction chemotherapy of two cycles of taxotere, cisplatin and 5-fluorouracil followed by radiotherapy plus weekly cetuximab. PATIENTS AND METHODS: Thirty-six patients with stage III or IV squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx were treated and evaluated for response and acute toxicity. RESULTS: Eighty-one percent of patients had stage IV disease and 42% had hypopharyngeal and oral cavity primaries. The overall response rate was 81.8%, with 60.6% complete response and 33.3% partial response. Severe toxicities were febrile neutropenia (6%) during induction chemotherapy and dermatitis (48%), mucositis (33%) and dysphagia (12%) during the concurrent phase. CONCLUSION: Our protocol proved to be feasible, effective and well tolerated. This sequential strategy should be further investigated.

Concomitant adjuvant chemoradiotherapy with weekly low-dose cisplatin for high-risk squamous cell carcinoma of the head and neck: a phase II prospective trial.

AIMS: Several randomised trials have tested adjuvant regimens using concomitant high-dose cisplatin and radiotherapy to improve outcome in high-risk locally advanced squamous cell head and neck cancer (HNSCC), showing a substantial increase in locoregional control and disease-free survival, despite a higher and eventually detrimental toxicity profile. The aim of the present phase II single-stage prospective study was to investigate whether a weekly cisplatin-based chemoradiotherapy regimen might be able to improve patients' compliance compared with standard-dose cisplatin with similar outcome results. MATERIALS AND METHODS: Between January 2004 and November 2008, 54 patients with high-risk locally advanced HNSCC were enrolled on to this phase II trial. Patient characteristics were: median age 59.7 years, Eastern Cooperative Oncology Group performance status 1 in 72% of patients and stage IV disease in 82%, extracapsular nodal spread in 67% and positive/close surgical margins in 37%. Patients received cisplatin (30 mg/m(2)) once a week for 7-8 weeks concurrent with external beam radiotherapy delivered with a median dose of 66.6 Gy (1.8 Gy each day; five fractions/week) on the primary site and 50 Gy (2 Gy each day) for the lower neck. RESULTS: Major acute toxicity of the combined treatment, defined as grade 3-4 mucositis, was observed in 35.2% of patients. No fatal complications occurred, with 81.5% of patients completing the planned regimen. Late reactions were mild (total 16% with a grade 3 dysphagia rate of 12%). The locoregional control rate was 82%; 5 year overall and disease-free survival were 63 and 62%, respectively. CONCLUSIONS: Concomitant adjuvant chemoradiotherapy with weekly cisplatin seems to be a feasible and well-tolerated therapeutic approach in 'unfit' patients. Clinical results seem to be at least comparable with those previously reported. However, to draw any definitive conclusion, large confirmatory phase III randomised trials are demanded.

Induction chemotherapy followed by concurrent chemoradiotherapy in advanced head and neck squamous cell carcinoma.

BACKGROUND: A phase II study was carried out to investigate an induction regimen with cisplatin, paclitaxel followed by radiotherapy concurrent with weekly cisplatin for locally advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Stage III-IV disease patients were eligible. Two cisplatin (100 mg/m2) and paclitaxel (175 mg/m2) courses were administered every 21 days followed by standard fractionated external beam radiotherapy (approximately 70 Gy), concomitant to weekly cisplatin (30 mg/m2). RESULTS: Thirty-five patients were enrolled: over 70% had unresectable disease with bulky lesions. Grade 3-4 neutropenia developed in 14% and G3 mucositis in 23%. Locoregional control was achieved in 51%. Median time to progression and overall survival were 10,7 and 17 months respectively; 2- and 3-year survival rates were 30% and 25% respectively. CONCLUSION: Our induction two-drug regimen followed by chemoradiotherapy with concurrent weekly cisplatin was well tolerated with low acute toxicity and good locoregional control and survival rate.

Impact event at the Permian-Triassic boundary: evidence from extraterrestrial noble gases in fullerenes.

The Permian-Triassic boundary (PTB) event, which occurred about 251.4 million years ago, is marked by the most severe mass extinction in the geologic record. Recent studies of some PTB sites indicate that the extinctions occurred very abruptly, consistent with a catastrophic, possibly extraterrestrial, cause. Fullerenes (C60 to C200) from sediments at the PTB contain trapped helium and argon with isotope ratios similar to the planetary component of carbonaceous chondrites. These data imply that an impact event (asteroidal or cometary) accompanied the extinction, as was the case for the Cretaceous-Tertiary extinction event about 65 million years ago.

[Prognostic factors in the treatment of advanced cervical cancer. A retrospective study]. / Fattori prognostici nel trattamento del cervicocarcinoma in stadio localmente avanzato. Studio retrospettivo.

BACKGROUND: The value of prognostic factors in patients with advanced cervix carcinoma treated by radiotherapy was assessed in a retrospective study. METHODS: From January 1977 through December 1990, 261 patients (average age 60 years) were treated at the Radiotherapy Department of the University of Turin. Distribution by stage was: 142 T2b (54%), 8 T3a (3%), 98 T3b (38%) and 13 T4 (5%). 83% of the patients underwent radiotherapy alone; the total dose was 45-88 Gy in 91 patients (42%) with poor clinical conditions, 60-75 Gy in 121 (56%) and 75-80 Gy in 5 cases. 17% of the patients was treated by surgery combined with radiotherapy. The median follow-up was 50 months (minimum 2, maximum 177 months). RESULTS: The 5-year NED survival and local control were 42% (52% for T2b, 33% for T3 and 15% for T4). The severe (G3-G4) complication rate was very low (1.9%). CONCLUSION: In our series, the prognostic factors which significantly influenced survival in the uni-variate analysis were: advanced T stage, contemporary infiltration of parametrium and vagina, nodal status, non squamous neoplasm, younger age and the absence of brachytherapy in the radiotherapy alone protocol.

Basic and clinical research for the new radiotherapy.

Basic research has allowed the full knowledge of the underlying mechanisms of the use of radiotherapy in cancer treatment. However, in spite of the crop of radiobiological studies, the impact on clinical research in last years has been relatively little. Within the recent research in man, studies on altered dose fractionations, combined radiation and chemotherapy together with the development of sophisticated technology have allowed the use of new methods of radiotherapy while those existing have been optimized.

Brachytherapy and local control.

Locoregional control of primary tumor is fundamental to cure since only in one third of patients the onset of distant metastases is the major cause of therapeutic failure. Thus recently, all therapeutic approaches aimed at the enhancement of locoregional control have been considered with growing interest. More particularly, brachytherapy alone or in combined modality therapy as an important option in the local treatment of various malignant tumors, has been widely used; this being related to the now available information on dose-rate, remote after-loading procedures, the new, safe and handy radionuclides and computerized dosimetry systems which allow a more accurate and rapid dose calculation. These advances have led to a wider application of brachytherapy. Together with the classical indications for head and neck and cervical tumors, brachytherapy plays now a well-established role in the treatment of breast, brain, gastrointestinal, genitourinary, soft tissue lung and eye tumors.

[Prognostic factors in the treatment of carcinoma of the cervix uteri in IB-IIA stage. Retrospective study]. / Fattori prognostici nel trattamento del carcinoma del collo dell'utero negli stadi IB-IIA. Studio retrospettivo.

January, 1977, to December, 1990, 311 patients with stage IB-IIA cervix carcinoma were treated at the Radiotherapy Department of the University of Turin. The distribution by stage was: 232 T1b (74.6%) and 79 T2a (25.4%). One hundred and eighty-nine patients (77% T1b-23% T2a) underwent preoperative radiotherapy, 63 patients (58% T1b-42% T2a) radiotherapy alone and 59 (85% T1b-15% T2a) postoperative radiotherapy. The first group of patients was treated according to three treatment protocols, based on different surgical procedures. During the median follow-up period of 86 months (82.6% of the patients underwent a minimum 3-year follow-up), 55 locoregional relapses (17%) and 21 extrapelvic metastases (7%) were observed. The 5-year NED survival rate and local control was 80%. The prognostic factors which significantly influenced survival in the univariate analysis, were: disease stage (p < .01), age (p < .05), the period between first symptom and therapy (p = .01), treatment protocols (radiotherapy combined with surgery versus radiation therapy alone: p < .05), residual disease after brachytherapy (p < .01), nodal status (p < .00001). In the radiotherapy alone group, the total dose influence on survival was not statistically significant (p = .12). In our series, histology and surgical procedures did not seem to influence prognosis. In the multivariate analysis, treatment protocol, age and residual disease after brachytherapy did not influence the prognosis, whereas the total dose of radiotherapy, pain (as first symptom) and Wertheim-Meigs surgery approach are prognostic factors. Severe late-effects were 17: 13 in the radiotherapy plus surgery protocol and 4 in the radiotherapy alone protocol. The incidence of major complications seems to correlate with surgical impact.

A unified theory of impact crises and mass extinctions: quantitative tests.

Several quantitative tests of a general hypothesis linking impacts of large asteroids and comets with mass extinctions of life are possible based on astronomical data, impact dynamics, and geological information. The waiting times of large-body impacts on the Earth derived from the flux of Earth-crossing asteroids and comets, and the estimated size of impacts capable of causing, large-scale environmental disasters, predict the impacts of objects > or = 5 km in diameter (> or = 10(7) Mt TNT equivalent) could be sufficient to explain the record of approximately 25 extinction pulses in the last 540 Myr, with the 5 recorded major mass extinctions related to impacts of the largest objects of > or = 10 km in diameter (> or = 10(8) Mt events). Smaller impacts (approximately 10(6) Mt), with significant regional environmental effects, could be responsible for the lesser boundaries in the geologic record. Tests of the "kill curve" relationship for impact-induced extinctions based on new data on extinction intensities, and several well-dated large impact craters, also suggest that major mass extinctions require large impacts, and that a step in the kill curve may exist at impacts that produce craters of approximately 100 km diameter, smaller impacts being capable of only relatively weak extinction pulses. Single impact craters less than approximately 60 km in diameter should not be associated with detectable global extinction pulses (although they may explain stage and zone boundaries marked by lesser faunal turnover), but multiple impacts in that size range may produce significant stepped extinction pulses. Statistical tests of the last occurrences of species at mass-extinction boundaries are generally consistent with predictions for abrupt or stepped extinctions, and several boundaries are known to show "catastrophic" signatures of environmental disasters and biomass crash, impoverished postextinction fauna and flora dominated by stress-tolerant and opportunistic species, and gradual ecological recovery and radiation of new taxa. Isotopic and other geochemical signatures are also generally consistent with the expected after-effects of catastrophic impacts. Seven of the recognized extinction pulses seem to be associated with concurrent (in some cases multiple) stratigraphic impact markers (e.g., layers with high iridium, shocked minerals, microtektites), and/or large, dated impact craters. Other less well-studied crisis intervals show elevated iridium, but well below that of the K/T spike, which might be explained by low-Ir impactors, ejecta blowoff, or sedimentary reworking and dilution of impact signatures. The best explanation for a possible periodic component of approximately 30 Myr in mass extinctions and clusters of impacts is the pulselike modulation of the comet flux associated with the solar system's periodic passage through the plane of the Milky Way Galaxy. The quantitative agreement between paleontologic and astronomical data suggests an important underlying unification of the processes involved.

The terminal Paleozoic fungal event: evidence of terrestrial ecosystem destabilization and collapse.

Because of its prominent role in global biomass storage, land vegetation is the most obvious biota to be investigated for records of dramatic ecologic crisis in Earth history. There is accumulating evidence that, throughout the world, sedimentary organic matter preserved in latest Permian deposits is characterized by unparalleled abundances of fungal remains, irrespective of depositional environment (marine, lacustrine, fluviatile), floral provinciality, and climatic zonation. This fungal event can be considered to reflect excessive dieback of arboreous vegetation, effecting destabilization and subsequent collapse of terrestrial ecosystems with concomitant loss of standing biomass. Such a scenario is in harmony with predictions that the Permian-Triassic ecologic crisis was triggered by the effects of severe changes in atmospheric chemistry arising from the rapid eruption of the Siberian Traps flood basalts.

Concomitant radiotherapy and daily low-dose carboplatin in locally advanced, unresectable head and neck cancer. Definitive results of a phase I-II study.

The combination of daily low-dose carboplatin and radiotherapy was studied in 55 patients with inoperable head and neck cancer. All patients were planned to receive 70 Gy plus carboplatin i.v. daily, 45-60 min before radiotherapy. A starting schedule of 30 mg/m2 on days 1 through 5, weeks 1, 3, 5 and 7 was administered to 17 patients; an escalating daily dose, up to 55 mg/m2, was given to 38 additional patients. Up to a daily dose of 45 mg/m2, only 4.4% of the patients developed grade 3 leukopenia; on the contrary, grade 3 and 4 leukopenia was seen in 62.5% of patients receiving 50 mg/m2 or more. Mucositis was the major nonhaematologic toxicity and seemed to be dose-dependent. At the end of the loco-regional treatment there were 33 (61.1%) CR and 17 PR; the most effective total carboplatin dose seemed to be 40-45 mg/m2. After surgical salvage the number of CRs increased to 37 (68.5%). One- and 2-year loco-regional control rates were 64% and 53% respectively. One- and 2-year actuarial survival rates were 71% and 53% respectively; the corresponding rates of disease-free survival were 60% and 43%. There was a strong correlation nodal status and both survival and disease-free survival.

[The surgical and radiotherapy treatment of endometrial adenocarcinoma. A retrospective analysis of 128 patients]. / Trattamento chirurgico e radioterapico dell'adenocarcinoma dell'endometrio. Analisi retrospettiva su 128 pazienti.

From January 1980 through December 1987, 128 endometrial carcinomas were treated with combined irradiation and surgery (101 cases) or with radiotherapy alone (27 patients). Mean follow-up was 5 years (range: 2-9). Actuarial disease-free (DF) survival (according to the Kaplan and Meyer method) was 86% for T1-T2 patients, 50% for T3 cases and 35% for T4. Recurrence rate was 20% (26 patients): 9 had local recurrences, 9 nodal relapses, and 8 distant metastases. Overall side-effects were observed in only 7/128 patients (5.4%): they were grade I in 6 cases and grade II in 1. The evaluation of the prognostic factors confirms the importance of: stage (disease-free survival at 5 years: 86% for T1-T2 versus 50-35% for T3-T4); uterus size in stage T1 (DF survival at 5 years: 90% for T1A versus 70% for T1B); grading (DF survival at 5 years: 92, 87, 62% for G1, G2, G3, respectively). Myometrial infiltration seems to have no prognostic value.

Interstitial brachytherapy for carcinomas of the lower lip. Results of treatment.

From 1973 to 1988 47 patients with previously untreated T1 and T2 squamous cell carcinomas of the lower lip received a definitive course of interstitial brachytherapy by iridium 192 wires. The disease stage was T1 in 21 cases (44.7%) and T2 in 26, and N0 in all cases except 2 of N1. Radiation therapy dose ranged between 6000 and 8000 cGy. Local control was obtained in 44 patients (93.6%). Treatment failure in the neck was observed in 3 patients (6.7%). The 5- and 10-year actuarial disease-free survival rates were 92% and 85%, respectively. A surgical salvage was attempted in 3 patients, with postoperative definitive control of the disease in 2. The 10-year actuarial overall survival was 95%. The incidence of complications was acceptable (10.6% of mucosal necrosis). An excellent or good cosmetic result was obtained in 91.7% of patients.

The mid-Cretaceous super plume, carbon dioxide, and global warming.

Carbon-dioxide releases associated with a mid-Cretaceous super plume and the emplacement of the Ontong-Java Plateau have been suggested as a principal cause of the mid-Cretaceous global warming. We developed a carbonate-silicate cycle model to quantify the possible climatic effects of these CO2 releases, utilizing four different formulations for the rate of silicate-rock weathering as a function of atmospheric CO2. We find that CO2 emissions resulting from super-plume tectonics could have produced atmospheric CO2 levels from 3.7 to 14.7 times the modern pre-industrial value of 285 ppm. Based on the temperature sensitivity to CO2 increases used in the weathering-rate formulations, this would cause a global warming of from 2.8 to 7.7 degrees C over today's global mean temperature. Altered continental positions and higher sea level may have been contributed about 4.8 degrees C to mid-Cretaceous warming. Thus, the combined effects of paleogeographic changes and super-plume related CO2 emissions could be in the range of 7.6 to 12.5 degrees C, within the 6 to 14 degrees C range previously estimated for mid-Cretaceous warming. CO2 releases from oceanic plateaus alone are unlikely to have been directly responsible for more than 20% of the mid-Cretaceous increase in atmospheric CO2.

[Total skin therapy with electron beams. I. Physical and geometric factors]. / Terapia cutanea totale con fasci di elettroni. Parte I. Fattori fisici e geometrici.

The study pf physical and geometrical factors influencing dose distribution is necessary in performing the Total Skin Electron Therapy. The authors examined some aspects. Photographic emulsions in humanoid phantom were used for dosimetry. The techniques uses 6 dual fields at 320 cm treatment distance, with a degrading lucite filter 100 x 200 x 0.6 cm3 at 20 cm from the patient. Absorbed dose and energy were determined according TG 30 and 21 AAPM. The position of degrading filter was recognized to be the main factor influencing dose rate, penetration depth and dose homogeneity.