Assessment of radiation-induced xerostomia: validation of the Italian version of the xerostomia questionnaire in head and neck cancer patients.

PURPOSE: Xerostomia is the most common acute and late side effect of radiation treatment for head and neck cancer. Affecting taste perception, chewing, swallowing and speech, xerostomia is also the major cause of decreased quality of life. The aims of this study were to validate the Italian translation of the self-reported eight-item xerostomia questionnaire (XQ) and determine its psychometric properties in patients treated with radiotherapy for head and neck cancer. METHODS: An observational cross-sectional study was conducted in the Radiotherapy Unit of the Veneto Institute of Oncology - IOV in Padua. The XQ was translated according to international guidelines and filled out by 102 patients. Construct validity was assessed using principal component analysis, internal consistency using Cronbach's α coefficient and test-retest reliability at 1-month interval using the intraclass correlation coefficient (ICC). Criterion-related validity was evaluated to compare the Italian version of XQ with the European Organization for Research and Treatment of Cancer (EORTC) Core Quality-of-Life Questionnaire (QLQ-C30) and its Head and Neck Cancer Module (QLQ-H&N35). RESULTS: Cronbach's α for the Italian version of XQ was strong at α = 0.93, test-retest reliability was also strong (0.79) and factor analysis confirmed that the questionnaire was one-dimensional. Criterion-related validity was excellent with high association with the EORTC QLQ-H&N35 xerostomia and sticky saliva scales. CONCLUSIONS: The Italian version of XQ has excellent psychometric properties and can be used to evaluate the impact of emerging radiation delivery techniques aiming at preventing xerostomia.

Predictive factors for oropharyngeal mycosis during radiochemotherapy for head and neck carcinoma and consequences on treatment duration. Results of mycosis in radiotherapy (MIR): a prospective longitudinal study.

BACKGROUND AND PURPOSE: Oropharyngeal mycosis (OPM) is a complication of radiotherapy (RT) treatments for head and neck (H&N) cancer, worsening mucositis and dysphagia, causing treatment interruptions and increasing overall treatment time. Prophylaxis with antifungals is expensive. Better patient selection through the analysis of prognostic factors should improve treatment efficacy and reduce costs. MATERIALS AND METHODS: A multicentre, prospective, controlled longitudinal study, with ethics committee approval, examined H&N cancer patients who were candidates for curative treatments with radio-chemotherapy. Patients were divided in groups according to OPM appearance: before the starting of RT (cases), during RT (new cases) and never (no cases). RESULTS: Of 410 evaluable patients, 20 were existing cases, 201 new cases and 189 did not report OPM. In our study OPM appears in 42.4% of people >70years and in 58.2% of younger individuals (p=0.0042), and in 68.6% of women versus 50.8% of men (p=0.0069). Mucositis and dysphagia were higher and salivation reduced among people with OPM (p<0.0000). Patients with OPM had longer hospitalization (p=0.0002) and longer (>12days) treatment interruptions (p=0.0288). CONCLUSIONS: Patients with OPM had higher toxicity and a greater number of long treatment interruptions. Analyses of prognostic factors can help clinicians understand OPM distribution and select patients with the highest probability of OPM for antifungal prophylaxis.

Application of an interstitial and biodegradable balloon system for prostate-rectum separation during prostate cancer radiotherapy: a prospective multi-center study.

BACKGROUND AND PURPOSE: Rectal toxicity presents a significant limiting factor in prostate radiotherapy regimens. This study evaluated the safety and efficacy of an implantable and biodegradable balloon specifically designed to protect rectal tissue during radiotherapy by increasing the prostate-rectum interspace. PATIENTS AND METHODS: Balloons were transperineally implanted, under transrectal ultrasound guidance, into the prostate-rectum interspace in 27 patients with localized prostate cancer scheduled to undergo radiotherapy. Patients underwent two simulations for radiotherapy planning--the first simulation before implant, and the second simulation seven days post implant. The balloon position, the dimensions of the prostate, and the distance between the prostate and rectum were evaluated by CT/US examinations 1 week after the implant, weekly during the radiotherapy period, and at 3 and 6 months post implant. Dose-volume histograms of pre and post implantation were compared. Adverse events were recorded throughout the study period. RESULTS: Four of 27 patients were excluded from the evaluation. One was excluded due to a technical failure during implant, and three patients were excluded because the balloon prematurely deflated. The balloon status was evaluated for the duration of the radiotherapy period in 23 patients. With the balloon implant, the distance between the prostate and rectum increased 10-fold, from a mean 0.22 ± 0.2 cm to 2.47 ± 0.47 cm. During the radiotherapy period the balloon length changed from 4.25 ± 0.49 cm to 3.81 ± 0.84 cm and the balloon height from 1.86 ± 0.24 cm to 1.67 ± 0.22 cm. But the prostate-rectum interspace distance remained constant from beginning to end of radiotherapy: 2.47 ± 0.47 cm and 2.41 ± 0.43 cm, respectively. A significant mean reduction in calculated rectal radiation exposure was achieved. The implant procedure was well tolerated. The adverse events included mild pain at the perineal skin and in the anus. Three patients experienced acute urinary retention which resolved in a few hours following conservative treatment. No infections or thromboembolic events occurred during the implant procedure or during the radiotherapy period. CONCLUSION: The transperineal implantation of the biodegradable balloon in patients scheduled to receive radiotherapy was safe and achieved a significant and constant gap between the prostate and rectum. This separation resulted in an important reduction in the rectal radiation dose. A prospective study to evaluate the acute and late rectal toxicity is needed.

Boron neutron capture therapy and 18F-labelled borophenylalanine positron emission tomography: a critical and clinical overview of the literature.

Positron emission tomography (PET) is considered one of the most useful tool for molecular imaging both in clinical and preclinical research for in vivo assessing of biochemical and pharmacological processes. Boron neutron capture therapy (BNCT) is a biologically-targeted radiotherapy that can selectively hit the tumour cells, saving the surrounding normal tissue. Boron 10 ((10)B) is the isotope widely used for this purpose, and acts as killer for tumor cells, releasing highly reactive α and (7)Li-particles when it absorbs a thermal neutron. The basic requirements for a successful BNCT treatment are firstly that the boron-containing compound/material has to be delivered to the neoplastic tissue, and secondly the amount of boron atoms concentrated inside/around the cancer cells must be sufficient for an optimal therapeutic response. The irradiation of tissue or organ with therapeutic doses of thermal neutrons can lead to a selective, complete ablation of the malignant lesion. Specific carriers have been developed for BNCT: para-borophenylalanine (BPA), represents one of them and the most employed in clinical trials to preferentially deliver boron to the malignancy. For the in vivo examination of pharmacokinetic, accumulation and metabolism characteristics of L-B-BPA, a positron-labeled boronophenylalanine analogue, L-(18)F-(10)BPA was proposed and its pharmaco-properties were non-invasively evaluated by PET imaging. Herein, we summarize BNCT principles and applications, boron carrier and boron imaging with PET, PET-guided BNCT and other studied and employed tracers for PET in order to optimizeBNCT.

Radiotherapy and temozolomide in anaplastic astrocytoma: a retrospective multicenter study by the Central Nervous System Study Group of AIRO (Italian Association of Radiation Oncology).

Although the evidence for the benefit of adding temozolomide (TMZ) to radiotherapy (RT) is limited to glioblastoma patients, there is currently a trend toward treating anaplastic astrocytomas (AAs) with combined RT + TMZ. The aim of the present study was to describe the patterns of care of patients affected by AA and, particularly, to compare the outcome of patients treated exclusively with RT with those treated with RT + TMZ. Data of 295 newly diagnosed AAs treated with postoperative RT ± TMZ in the period from 2002 to 2007 were reviewed. More than 75% of patients underwent a surgical removal. All the patients had postoperative RT; 86.1% of them were treated with 3D-conformal RT (3D-CRT). Sixty-seven percent of the entire group received postoperative chemotherapy with TMZ (n = 198). One-hundred sixty-six patients received both concomitant and sequential TMZ. Prescription of postoperative TMZ increased in the most recent period (2005-2007). One- and 4-year survival rates were 70.2% and 28.6%, respectively. No statistically significant improvement in survival was observed with the addition of TMZ to RT (P = .59). Multivariate analysis showed the statistical significance of age, presence of seizures, Recursive Partitioning Analysis classes I-III, extent of surgical removal, and 3D-CRT. Changes in the care of AA over the past years are documented. Currently there is not evidence to justify the addition of TMZ to postoperative RT for patients with newly diagnosed AA outside a clinical trial. Results of prospective and randomized trials are needed.

Long-term results in childhood rhabdomyosarcoma: a report from the Italian Cooperative Study RMS 79.

BACKGROUND: The results obtained by protocols for children with rhabdomyosarcoma (RMS) have improved in recent decades. Survival curves usually reach a plateau 3 years after the diagnosis, suggesting that long-term survival can be expected, but late events are known to occur. We analyzed the long-term results of the RMS 79 protocol to investigate the type and impact of such events. PROCEDURE: From 1979 to 1987, 163 children with RMS diagnosed at 21 Italian institutions were registered. Each institution was contacted every year to record patients' status after the end of treatment. When patients were lost to follow-up, their status was checked by inquiring at the Registry Offices of the towns of residence and the cause of death or occurrence of second cancers was investigated by contacting the patients or their family by phone. RESULTS: Overall, 16 patients had late events, that is, 7 tumor recurrences, 6 second tumors, and 3 deaths due to treatment-related complications. The overall survival rates dropped from 62.6 at 3 years to 52.8 at 20 years. By multivariate analysis, the characteristics influencing long-term survival were histology, tumor site and size, and IRS group. Factors predictive of any kind of late event were tumor site and IRS group. CONCLUSIONS: Major late events can significantly affect the long-term survival of children with RMS. Modern protocols should provide for a much longer follow-up than is usually considered to confirm the results achieved and enable possible correlations between primary treatment and late events to be investigated.

Follicular thyroid carcinoma with metastases to the pituitary causing pituitary insufficiency.

BACKGROUND: Pituitary metastases are found in about 1% of all pituitary resections. They often derive from breast, lung, and gastroenteric tract adenocarcinomas, very rarely from thyroid carcinoma. Presenting symptoms of thyroid carcinoma metastatic to the pituitary gland are usually chiasmatic with central neurological impairment due to space-occupying expansion in the parasellar region. Hypopituitarism is more often associated with papillary and medullary rather than follicular thyroid carcinoma (FTC). Here we describe a patient with pituitary metastasis from FTC who had hypopituitarism with thyrotropin (TSH) deficiency. SUMMARY: A 61-year-old woman, who presented with visual deficits and pain to the right orbit, was found on magnetic resonance imaging to have a large mass involving the pituitary gland. She was found to have pituitary insufficiency based on corticotropin-releasing hormone and TSH-releasing hormone testing. Transnasopharyngeal biopsy of the mass revealed metastases from FTC. After total thyroidectomy, which confirmed widely invasive FTC, the patient underwent external beam radiation therapy of the metastases for progressive neurological symptoms and an increase in orbit pain. Since endogenous TSH production was insufficient, we used recombinant human TSH (rhTSH) as preparation for a series of radioiodine treatments. rhTSH administration, followed by 7.4 GBq of (131)I, was repeated seven times over a 10-year period. This was associated with a marked decrease in serum thyroglobulin levels accompanied by substantial clinical improvement, but after 7 years disease progression occurred. CONCLUSIONS: Seven patients with pituitary metastases from FTC have been reported. In all cases, some neurological signs and symptoms related to mass effect were reported, but no pituitary insufficiency was described. This may be the first case of FTC with metastases to the pituitary causing hypopituitarism. It seems likely that management of such cases could be limited to biopsy to confirm thyroid carcinoma, rather than more extensive surgery, and that this could be followed by multiple treatments with rhTSH followed by (131)I.

Tumour markers and FDG PET/CT for prediction of disease relapse in patients with breast cancer.

PURPOSE: The aim of the study was to assess the role of CA 15.3, CT and positron emission tomography (PET)/CT in patients with breast cancer and suspected disease relapse after primary treatment. METHODS: We studied 111 consecutive patients (mean age 61 ± 12 years) with previous breast cancer, already treated and with clinical or biochemical suspicion of disease relapse. All patients underwent CT and (18)F-fluorodeoxyglucose (FDG) PET/CT. In all patients, the value of CA 15.3 was compared to PET/CT and CT. The final diagnosis of relapse was established by invasive and noninvasive follow-up and was compared with CA 15.3, CT and PET/CT results. Univariate and multivariate analyses were used to identify the independent predictors of disease relapse and receiver-operating characteristic (ROC) curve for the identification of optimal CA 15.3 cutoff. RESULTS: Of all patients, 40 (36%) showed an increased CA 15.3 value, CT was positive in 73 (66%), whereas at PET/CT imaging 64 (58%) showed positive findings for disease relapse. Of 40 patients with increased marker levels, 22 patients had positive CT and 30 positive PET/CT (55 vs 75%, p < 0.001). At the end of follow-up, recurrence occurred in 32 (29%) patients, 16 (50%) of whom showed high levels of CA 15.3. PET/CT predicted relapse in 26 (81%) patients, whereas CT correctly identified 23 (72%). At univariate analysis, recurrence was significantly associated with high CA 15.3 values (p < 0.05) and positive PET/CT (p < 0.005). At multivariable analysis only positive PET/CT remained an independent predictor of disease relapse (p < 0.05). ROC analysis showed an optimal cutoff point for CA 15.3 of 19.1 U/ml (AUC 0.65, p < 0.01) to individuate positive PET/CT. CONCLUSION: FDG PET/CT is more sensitive than CT and CA 15.3 in the evaluation of disease relapse. PET/CT might be considered a complementary imaging technique during follow-up in patients with breast cancer.

Patterns of care and survival in a retrospective analysis of 1059 patients with glioblastoma multiforme treated between 2002 and 2007: a multicenter study by the Central Nervous System Study Group of Airo (italian Association of Radiation Oncology).

OBJECTIVE: To investigate the pattern of care and outcomes for newly diagnosed glioblastoma in Italy and compare our results with the previous Italian Patterns of Care study to determine whether significant changes occurred in clinical practice during the past 10 years. METHODS: Clinical, pathological, therapeutic, and survival data regarding 1059 patients treated in 18 radiotherapy centers between 2002 and 2007 were collected and retrospectively reviewed. RESULTS: Most patients underwent both computed tomography and magnetic resonance imaging either preoperatively (62.7%) or postoperatively (35.5%). Only 123 patients (11.6%) underwent a biopsy. Radiochemotherapy with temozolomide was the most frequent adjuvant treatment (70.7%). Most patients (88.2%) received 3-dimensional conformal radiotherapy. Median survival was 9.5 months. Two- and 5-year survival rates were 24.8% and 3.9%, respectively. Multivariate analysis showed the statistical significance of age, postoperative Karnofsky Performance Status scale score, surgical extent, use of 3-dimensional conformal radiotherapy, and use of chemotherapy. Use of a more aggressive approach was associated with longer survival in elderly patients. Comparing our results with those of the subgroup of patients included in our previous study who were treated between 1997 and 2001, relevant differences were found: more frequent use of magnetic resonance imaging, surgical removal more common than biopsy, and widespread use of 3-dimensional conformal radiotherapy + temozolomide. Furthermore, a significant improvement in terms of survival was noted (P < .001). CONCLUSION: Changes in the care of glioblastoma over the past few years are documented. Prognosis of glioblastoma patients has slightly but significantly improved with a small but noteworthy number of relatively long-term survivors.

Preoperative concomitant chemo-radiotherapy in superior sulcus tumour: A mono-institutional experience.

UNLABELLED: Superior sulcus tumour (SST) is an uncommon neoplasia whose optimal treatment remains controversial. Usually resected after induction RT or treated with definitive chemo-radiotherapy, it has recently aroused more interest because of preoperative chemo-radiotherapy. Treatment consisted of a platinum-based chemotherapy: carboplatin AUC 5 on days 1 and 22, combined with mitomycin-C 8 mg/m(2) on days 1 and 22, and vinblastine 4 mg/m(2) on days 1, 8, 22 and 29 (MVC) from 1994 to 1999, or combined with navelbine 25mg/m(2) on days 1, 8, 22 and 29 (NC), from 2000 to 2007. Radiotherapy was administered 5 days/week, 30 Gy in 10 fractions on days 22-35 (from 1994 to 1996), or 44 Gy in 22 fractions on days 22-52 (from 1997 to 2007). SURGERY was planned after 2-3 weeks since the completion of radiotherapy. Since 1994, 37 pts were treated with induction chemo-radiotherapy, 1 with induction radiotherapy only. Induction chemotherapy: 16 pts had MVC (43%) and 21 NC (57%); induction radiotherapy: 7 patients treated with MVC had 30 Gy/10F, 9 had 44 Gy/22F; all the patients treated with NC had 44 Gy/22F, but 2 of them did not complete radiotherapy because of early death (after 16 Gy/8F) and toxicity (after 38 Gy/19F). Grade 3-4 haematological toxicity of induction chemo-radiotherapy was found in 13 patients (35%); the most frequent non-haematological toxicities were constipation and oesophagitis. One complete, 18 partial and 8 minimal responses/stable disease were observed. Moreover, 1 progression disease and 1 early death occurred. SURGERY: 30 upper lobectomies (17 right, 13 left) and 4 segmentectomies, with chest wall resections, were performed (89% resection rate); 4 pts were not operated. Radical resections were achieved in 74% of the patients, with 5 pathologic complete remissions at resection. Twenty-seven patients (71%) had improvement of shoulder/arm pain. Median progression-free survival was 64 weeks and median survival was 148 weeks. The 5-year overall and progression-free survivals were 40% and 29%, respectively. In the multimodality treatment of SST, concurrent carboplatin-based chemotherapy plus radiotherapy were active and feasible without major toxicities. This resulted in high resectability rate and favourable progression-free and overall survival rates.

Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: correlation With MGMT promoter methylation status.

PURPOSE: The aim of the present study was to evaluate factors predicting the recurrence pattern after the administration of temozolomide (TMZ), initially concurrent with radiotherapy (RT) and subsequently as maintenance therapy, which has become standard treatment for patients with newly diagnosed glioblastoma (GBM). PATIENTS AND METHODS: Ninety-five patients with newly diagnosed GBM were treated with RT plus TMZ (75 mg/m(2)/d) followed by maintenance TMZ cycles (150 to 200 mg/m(2) for 5 days every 28 days). Assessable MGMT methylation status and magnetic resonance imaging follow-up were mandatory in all cases. RESULTS: After a median follow-up of 18.9 months (range, 6.6 to 44.8 months), 79 patients (83%) had recurrence: inside the RT field in 57 patients (72.2%), outside in 17 patients (21.5%), and at RT margin in five patients (6.3%). MGMT status was correlated with the site of recurrence, which occurred inside, or at the margin of, the RT field in 51 patients (85%) with MGMT unmethylated status and in 11 patients (57.9%) with MGMT methylated status (P = .01). Recurrences outside the RT field occurred after a longer time interval than those inside the RT field (14.9 v 9.2 months, P = .02). CONCLUSION: After the administration of TMZ concomitant with and adjuvant to RT in patients with GBM, the pattern of, and time to, recurrence are strictly correlated with MGMT methylation status.

Improved survival for children with parameningeal rhabdomyosarcoma: results from the AIEOP soft tissue sarcoma committee.

BACKGROUND: Parameningeal rhabdomyosarcoma (PM-RMS) is a rare, highly malignant pediatric tumor arising from locations adjacent to the meninges, from where it can spread intracranially. PROCEDURE: We reviewed 109 children with non-metastatic PM-RMS enrolled in the Italian RMS79, RMS88 and RMS96 protocols over a 24-year period. All patients received intensive chemotherapy and standard or hyperfractionated and accelerated radiotherapy. Some had delayed surgery. RESULTS: Five-year overall survival rose from 40% in the RMS79 to 72% in the RMS88 and RMS96 protocols (P = 0.01), where more intensive chemotherapy and hyperfractionated accelerated radiotherapy (HART) was used. Delayed surgery after initial treatment was statistically associated with a better prognosis. Unfavorable tumor characteristics for RMS arising in other sites, for example, histology, invasiveness or node involvement, did not predict outcome for PM-RMS. CONCLUSION: Outcome in PM-RMS patients enrolled in three consecutive Italian protocols has progressively improved, as a result of intensive chemotherapy, delayed surgery and, possibly, HART, though improved imaging and radiotherapeutic tools may have had a role as well.

Tumour-localizing and -photosensitising properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H2TCP).

A water-soluble meso-substituted porphyrin (H(2)TCP) bearing 36 boron atoms, which appeared to be an efficient photodynamic sensitiser (singlet oxygen quantum yield=0.44), was studied for its accumulation by murine melanotic melanoma cells (B16F1). The amount of H(2)TCP in the cells increased with the porphyrin dose in the incubation medium up to, and at least, 100 microM concentrations with no significant cytotoxic effect in the dark. Moreover, the H(2)TCP uptake increased with the incubation time reaching a plateau value corresponding with the recovery of 0.4 nmol of H(2)TCP per mg of cell proteins after 24h incubation. Fluorescence microscopy observations showed that the porphyrin was largely localized intracellularly, exhibiting a discrete distribution in the cytoplasm with a pattern which was closely similar to that observed for the endosomal probe Lucifer yellow. The photosensitising efficiency of the H(2)TCP toward B16F1 cells was studied for different irradiation (1-15 min) and incubation (1-24 h) times. Nearly complete (>95%) cell mortality was obtained upon incubation with 20 microM H(2)TCP and 10 min irradiation with red light (600-700 nm, 20 mW/cm(2)). The porphyrin was also accumulated in appreciable amounts by the tumour tissue after intravenous injection to C57BL/6 mice bearing a subcutaneously transplanted melanotic melanoma. Maximum accumulation in the tumour was achieved by administration of H(2)TCP dissolved in the ternary mixture 20% dimethylsulfoxide (DMSO)-30% polyethyleneglycol (PEG 400)-50% water. Thus, this porphyrin could act as both a photodynamic therapy agent and a radiosensitising agent for boron neutron capture therapy.

Determining therapeutic approaches in the elderly with rectal cancer.

BACKGROUND: To evaluate the toxicity and feasibility of pelvic radiotherapy (RT) and/or surgery in elderly patients with locally advanced low-lying rectal cancer. PATIENTS AND METHODS: From November 1999 to November 2005, 51 patients aged >or=70 years who underwent RT for locally advanced low-lying rectal cancer were retrospectively examined. Variables considered were age, co-morbidities (evaluated according to the Charlson score and the Cumulative Illness Rating Scale-Geriatric [CIRS-G] score) and surgery versus no surgery. RESULTS: The median age was 80 years (range 70-94 years) and the male : female ratio was 33 : 18. A total of 5.9% of patients were considered 'fit', 72.5% had one or more CIRS-G grade 1 or 2 co-morbidities and 21.6% had one or more CIRS-G grade 3 co-morbidities. 54.9% of patients underwent surgery and 45.1% underwent RT. Only 9 of 21 (42.8%) patients who underwent radical resection received the full course of adjuvant RT and only seven (50%) of all patients treated with RT alone received the full dose of therapy. Patients with one or more CIRS-G grade 3 co-morbidities reported similar numbers of grade 1-2 toxicities as patients with one or more CIRS-G grade 2 co-morbidities. CONCLUSION: Notwithstanding the small number of patients analysed, the findings of this study indicate that elderly patients with rectal cancer and mild co-morbidities could probably receive the same treatment as fit elderly patients, given that tolerability appeared to be similar in both categories of patients. Neither age nor co-morbidities should be considered reasons to deny the patient the possible benefits of receiving complete treatment. Moreover, Multidimensional Geriatric Assessment should always be undertaken to help clinicians make better decisions about treatment. Further prospective trials are needed to confirm these results.

Long-term survival of patients treated with photodynamic therapy for carcinoma in situ and early non-small-cell lung carcinoma.

PURPOSE: The role of photodynamic therapy (PDT) in the treatment of small cancers has been established in several clinical studies. Here, we report on the efficacy of PDT for early inoperable or recurrent non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: From June 1989 to November 2004, 40 patients with 50 NSCLC were treated with PDT. Twelve cases were inoperable for medical reasons and were staged as T1N0M0, and 28 had recurrent in situ carcinoma. Patients with residual disease after PDT received definitive radiotherapy and/or brachytherapy. Follow-up ranged from 6 to 167 months (median 43.59). Twenty of the 40 patients received i.v. injections of hematoporphyrin derivative (5 mg/kg), the other 20 had injections of porfimer sodium (Photofrin, 2 mg/kg). An argon dye laser (630 nm wavelength, 200-300 J/cm2) was used for light irradiation in 24 of the 40 patients, a diode laser (Diomed, 630 nm wavelength, 100-200 J/cm2) in the other 16. RESULTS: PDT obtained a 72% complete response (CR) rate (36/50 treated lesions), that is 27 CR among the 37 Tis carcinomas and 9 among the 13 T1 cases. Kaplan-Meier curves showed a mean overall survival (OS) of 75.59 months (median 91.4 months). Two- and 5-year OS rates were 72.78% and 59.55%. The mean and median survival rates for patients with Tis stage were 86.5 and 120.4 months, respectively (standard error 9.50) and for patients with T1 disease they were 45.78 and 35.71 months, respectively; the difference was statistically significant (P = 0.03). No severe early or late PDT-related adverse events were recorded. CONCLUSIONS: PDT is effective in early primary or recurrent NSCLC, resulting in a CR rate of 72%. The incorporation of PDT in standard clinical practice, in combination with radiotherapy, warrants further investigation.

Primary rectal carcinoma in patients with stage IV resectable disease at diagnosis.

BACKGROUND: Rectal cancer is commonly diagnosed at a precocious stage, but for patients presenting at diagnosis with stage IV disease the best treatment is still undefined. The purpose of this study was to review the feasibility and outcome of multimodality treatment of rectal cancer patients metastatic at diagnosis. PATIENTS AND METHODS: From January 2000 to December 2005, 40 patients with histologically proven stage IV rectal adenocarcinoma (< 12 cm from the anal verge) were examined. Variables considered were age (under or over 65 years), tumour grade, presence of peritoneal carcinomatosis, type of surgery (palliative versus resection). RESULTS: The median age was 61 years (range, 32-83) and 27 were male and 13 female. Seventeen patients with unresectable or potentially resectable metastatic disease received neoadjuvant chemoradiotherapy (CHT-RT) with 5-fluorouracil (5FU) (plus oxaliplatin in 11 cases), radical surgery was performed in almost half of the cases; only in two patients were metastases also resected. If the patient is a candidate for radical surgical resection, the primary tumour should initially be treated as in a patient without metastatic disease and subsequently the primary tumour and metastases should be treated surgically. If the metastases are unresectable, the treatment of the primary lesion, according to the patient's symptoms, should be by palliative CHT. It is still not determined whether RT should be reserved for the symptomatic cases as an alternative to local surgery. In five patients treated with neoadjuvant CHT alone, radical local surgery was performed in two cases. Eighteen symptomatic patients were resected primarily; all of them received a postoperative CHT but only five of them also received postoperative RT. Nevertheless, after a multimodality treatment (neoadjuvant CHT +/- RT) 22.5% achieved a response rate (RR) (one complete remission (CR) and eight partial remission (PR)). Considering that all except two of the patients were locally radically resected and two of them also underwent metastases surgery, the overall RR was 17.5% (four CR and three PR). All of the CR were disease-free and alive after a median follow-up of 19.3 months. Age > or = 65 years had no impact on overall survival (OS), but the presence of peritoneal carcinosis in five patients showed a trend towards diminished survival, although it was not statistically significant (p = 0.08). CONCLUSION: The best treatment on diagnosis of metastatic rectal cancer is a multimodality CHT-RT approach. New prospective studies should evaluate non cross-resistant regimens as additional therapy for those patients with a systemic residual disease after common CHT-RT.

Primary mediastinal large B-cell lymphoma: results of intensive chemotherapy regimens (MACOP-B/VACOP-B) plus involved field radiotherapy on 53 patients. A single institution experience.

PURPOSE: The optimal therapy for primary mediastinal large B-cell lymphoma (PMLBCL) remains undefined. The superiority of intensive chemotherapy regimens (Methotrexate, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, Bleomycin [MACOP-B]/Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, Bleomycin [VACOP-B]) over Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP)-like chemotherapy is upheld by some authors. The role of radiotherapy is still debated. In the absence of randomized trials, we report clinical findings and treatment response in 53 consecutive patients treated with intensive chemotherapy and mediastinal involved-field radiation therapy (IFRT). METHODS AND MATERIAL: Fifty-three consecutive patients with PMLBCL were retrospectively analyzed. Planned treatment consisted of induction chemotherapy (I-CT; Prednisone, Methotrexate, Doxorubicin, Cyclophosphamide, Etoposide-Mechloroethamine, Vincristine, Procarbazine, Prednisone [ProMACE-MOPP] in the first 2 patients, MACOP-B in the next 11, and VACOP-B in the last 40) followed by IFRT. Planned treatment was concluded in 43 of 53 patients; in 10 patients, I-CT was not immediately followed by IFRT. Among these 10 patients, 6 received high-dose chemotherapy (HD-CT) followed by IFRT, 2 received HD-CT, and 2 received no further treatment. RESULTS: After a median follow-up of 93.9 months (range, 6-195 months), 45 of 53 patients (84.9%) were alive without disease. Eight patients died: 7 of PMLBCL and 1 of toxicity during HD-CT. The 5-year disease-free survival (DFS) and overall survival rates were 93.42% and 86.6%, respectively. The response rates after I-CT were complete response (CR) in 20 (37.73%) and partial response (PR) in 30 (56.60%); 3 patients (5.66%) were considered nonresponders. Among patients in PR after chemotherapy, 92% obtained a CR after IFRT. CONCLUSIONS: Our report confirms the efficacy of intensive chemotherapy plus mediastinal IFRT. IFRT plays a pivotal role in inducing CR in patients in PR after chemotherapy.

Treatment of chemotherapy-induced oral mucositis with light-emitting diode.

OBJECTIVE: The aim of this study was to assess the clinical effectiveness of phototherapy with noncoherent light in the alleviation of chemotherapy-induced mucositis in patients with metastatic cancer. BACKGROUND DATA: Mucositis occurs in more than 40% of chemotherapy-treated patients, significantly reducing the quality of their lives. Many different interventions have been evaluated to reduce oral mucositis. Recently, good results have been achieved by phototherapy with photoradiation, a technique which has virtually no side effects. Some clinical results seem to indicate that also phototherapy through noncoherent light emissions which can be produced by less expensive light sources such as light-emitting diodes (LEDs) may be effective. However, until now, no studies have been available on this subject. METHODS: Twelve patients, aged from 34 to 82, selected on the basis of a diagnosis of chemotherapy-induced oral mucositis, were treated intra-orally through a noncoherent LED emission, wavelength 645 +/- 15 nm, 7.8 mW, fluence 0.99 J/cm(2), three times a day for 1 week. Mucositis was scored daily using the Daily Mucositis Index (DMI), a scale that evaluates the disease evolution through 16 different items. The primary end-point assessed was the time to recovery, from the start of LED treatment, compared to a nonrandomized control group of 12 patients with comparable stomatitis. RESULTS: The median healing time, expressed as the DMI decrease, was 1.7 (range 1-2.8) and, in seven LED-treated patients, was shorter than in the control group. The healing rate (measured as the ratio of the DMIs) increased from 117% to 164%. CONCLUSION: This pilot study shows that LED treatment is safe and capable of reducing the duration of chemotherapy-induced mucositis. This result needs to be confirmed in an adequate phase III study.

Survival following adjuvant PCV or temozolomide for anaplastic astrocytoma.

We compared survival in patients with anaplastic astrocytoma (AA) treated with adjuvant procarbazine, lomustine, and vincristine (PCV) with survival in patients treated with temozolomide. A retrospective analysis was made of patients with newly diagnosed AA treated with adjuvant postradiotherapy chemotherapy. Outcome analysis included progression-free survival and overall survival. The following prognostic factors were taken into account: patient age, extent of resection, performance status, presence of contrast enhancement in presurgical imaging, and type of adjuvant treatment. Among 109 AA patients, 49 were treated with PCV and 60 with temozolomide. The treatment groups were well matched for pretreatment characteristics, except for the presence of contrast enhancement. Age, extent of surgery, performance status, and presence of contrast enhancement were statistically significant prognostic factors according to the Cox model analysis of survival. Type of adjuvant chemotherapy was not a significant factor, either for progression-free survival or for overall survival. Hematological toxicity, nonhematological toxicity grades 3-4, and premature discontinuation due to toxicity were observed in 9%, 3% to 5%, and 37%, respectively, of cases in the PCV group versus 4% to 5%, 0, and 0, respectively, in the temozolomide group. Although the present study was not randomized, it was well designed, and it reports on two homogeneous and consecutive series of patients, for whom histology was verified to obtain survival data only for patients with AA following the recent WHO 2000 classification. Even if no survival advantage has been demonstrated for temozolomide versus PCV, we conclude that temozolomide should be preferred because of its greater tolerability.