Clinical application of MOSkin dosimeters to rectal wall in vivo dosimetry in gynecological HDR brachytherapy.

PURPOSE: Three MOSkins dosimeters were assembled over a rectal probe and used to perform in vivo dosimetry during HDR brachytherapy treatments of vaginal cancer. The purpose of this study was to verify the applicability of the developed tool to evaluate discrepancies between planned and measured doses to the rectal wall. MATERIALS AND METHODS: MOSkin dosimeters from the Centre for Medical Radiation Physics are particularly suitable for brachytherapy procedures for their ability to be easily incorporated into treatment instrumentation. In this study, 26 treatment sessions of HDR vaginal brachytherapy were monitored using three MOSkin mounted on a rectal probe. A total of 78 measurements were collected and compared to doses determined by the treatment planning system. RESULTS: Mean dose discrepancy was determined as 2.2±6.9%, with 44.6% of the measurements within ±5%, 89.2% within ±10% and 10.8% higher than ±10%. When dose discrepancies were grouped according to the time elapsed between imaging and treatment (i.e., group 1: ≤90min; group 2: >90min), mean discrepancies resulted in 4.7±3.6% and 7.1±5.0% for groups 1 and 2, respectively. Furthermore, the position of the dosimeter on the rectal catheter was found to affect uncertainty, where highest uncertainties were observed for the dosimeter furthest inside the rectum. CONCLUSIONS: This study has verified MOSkin applicability to in-patient dose monitoring in gynecological brachytherapy procedures, demonstrating the dosimetric rectal probe setup as an accurate and convenient IVD instrument for rectal wall dose verification. Furthermore, the study demonstrates that the delivered dose discrepancy may be affected by the duration of treatment planning.

Italian version of the M.D. Anderson Symptom Inventory--Head and Neck Module: linguistic validation.

BACKGROUND: Head and neck cancer (HNC) patients can experience symptoms due to the tumor itself or to the treatment, with an impact on health-related quality of life (HRQoL). Patient-reported outcome (PRO) measures pertaining to HRQoL are used in medical research and to support clinical decisions. PRO instrument applicability and cultural adaptation must be tested for each population. The aim of this study is to linguistically validate the Italian translation of the M.D. Anderson Symptom Inventory--Head and Neck Module (MDASI-HN). METHODS: Following forward and backward translation of the items of the English MDASI-HN into Italian, it was administered along with a cognitive debriefing to HNC patients able to read and understand Italian language. Individual and group responses are presented using descriptive statistics. RESULTS: From May 2013 through September 2013, 56 patients with HNC (18 during curative treatment, 20 in palliative chemotherapy, and 18 in follow-up period) completed the MDASI-HN followed by accompanying cognitive debriefing. Ninety-nine percent of the individual MDASI-HN items were completed. Average time to complete the MDASI-HN was 8.5 min (range 3-15). Results suggested overall ease of completion, relevance, and comprehensibleness of this translated self-report instrument in this Italian patient population. CONCLUSIONS: The Italian version of the MDASI-HN is linguistically valid; future research should explore dimensionality, reliability, and convergent, discriminant, and predictive validity of this patient-reported instrument, in order to use this translated version in outcomes research and clinical settings.

Treatment-related outcome of oropharyngeal cancer patients differentiated by HPV dictated risk profile: a tertiary cancer centre series analysis.

BACKGROUND: To date, no treatment modality has been identified as more effective for oropharyngeal cancer (OPC), and no predictive factors are known to guide treatment decision for this disease. This retrospective study evaluates the differential effects of diverse treatment options for OPC according to patient risk profiles. PATIENTS AND METHODS: We considered two series of locally advanced squamous cell OPC patients treated with either surgery followed by radiotherapy (surgical series) or chemoradiation (CRT) with/without induction docetaxel, cisplatin and 5-fluorouracil (TPF) chemotherapy (CRT series). Smoking habits, tumor p16 expression/human papillomavirus (HPV) status and T and N stage were analyzed to stratify the patients according to Ang's risk profile (low, intermediate and high risk). Overall survival (OS) and disease-free survival were calculated with the Kaplan-Meier method. RESULTS: Globally, 171 patients were considered, 56 in surgical and 115 in CRT series. Patients were stratified in low- (20% of surgical and CRT groups), intermediate- (23% and 41%) and high-risk (57% and 39%) groups. In the surgical series, 5-year OS was 54.5%, 46.9% and 40.0% in low, intermediate and high Ang's risk profiles, respectively, whereas in the CRT series those were 100%, 78.9% and 46.7%, respectively. In the multivariable analyses, adjusting for inhomogeneity between the treatment group, the CRT effect was significantly higher in the low- and intermediate-risk groups (P-value for the interaction treatment risk group = 0.034 in the OS analysis). CONCLUSIONS: In this retrospective analysis, low- and intermediate-risk OPC patients had a better survival when treated with CRT compared with open surgery followed by radiation therapy. These data suggest that different treatment approaches might be essential in determining outcome results.

Preoperative chemotherapy in advanced resectable OCSCC: long-term results of a randomized phase III trial.

BACKGROUND: Data on preoperative chemotherapy in resectable oral cavity cancer are conflicting. We present the long-term results of a randomized trial of induction chemotherapy in resectable oral cavity cancer. PATIENTS AND METHODS: A randomized, parallel, multicentre trial evaluated the impact of three cycles of cisplatin 100 mg/m2 and fluorouracil 1000 mg/m2 (120-h infusion administered every 21 days) in stage T2-T4, N0-N2, previously untreated patients with advanced disease. Control group received upfront surgery. Postoperative radiation was offered to both arms when pathologic risk features were identified. The co-primary end points were the occurrence of locoregional or distant tumour relapse, and death. RESULTS: Among the 198 enrolled patients, with a median follow-up of 11.5 years, there was no difference in the incidence of locoregional relapse between chemotherapy and control group (P=0.6337), nor in distant metastasis development (P=0.1527). There was also no difference between groups in overall survival (P=0.3402). Patients with a pathological complete response (pCR) had higher probability of survival than those without (10-year OS: 76.2% versus 41.3%, P=0.0004). Late toxicities in patients with a minimum follow-up of 60 months (42 in each group) were similar between arms, except from fibrosis (cumulative incidence 40% versus 22% in chemotherapy arm) and grade 2 dysphagia (14% versus 5%). CONCLUSIONS: Long-term follow-up of this randomized trial confirmed the absence of survival benefit with preoperative chemotherapy in oral cavity cancer. Late toxicity was similar in the two arms except for fibrosis and dysphagia, which were less in the chemotherapy arm. The survival benefit for patients achieving a pCR was maintained.

Solid state TL detectors for in vivo dosimetry in brachytherapy.

In vivo dosimetry provides information about the actual dose delivered to the patient treated with radiotherapy and can be adopted within a routinary treatment quality assurance protocol. Aim of this study was to evaluate the feasibility of performing in vivo rectal dosimetry by placing thermoluminescence detectors directly on the transrectal ultrasound probe adopted for on-line treatment planning of high dose rate brachytherapy boosts of prostate cancer patients. A suitable protocol for TLD calibration has been set up. In vivo measurements resulted to be in good agreement with the calculated doses, showing that the proposed method is feasible and returns accurate results.

Docetaxel, cisplatin and 5-fluorouracil-based induction chemotherapy followed by intensity-modulated radiotherapy concurrent with cisplatin in locally advanced EBV-related nasopharyngeal cancer.

BACKGROUND: This monocentric study evaluates the activity and tolerability of docetaxel (Taxotere), cisplatin and 5-fluorouracil (5-FU) (TPF) induction chemotherapy followed by intensity-modulated radiotherapy (IMRT) concurrent with high-dose cisplatin in Epstein-Barr virus -related locally advanced undifferentiated nasopharyngeal cancer. PATIENTS AND METHODS: We retrospectively reviewed the records of patients who received induction docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, and 5-FU 750 mg/m(2)/day (96-h continuous infusion). Following induction, patients received full doses of IMRT concurrently with cisplatin 100 mg/m(2) every 21 days for three cycles. RESULTS: Thirty patients received three TPF cycles (median). Induction was well tolerated; the main toxicity was neutropenia (33%, grade 3-4). During chemoradiotherapy, neutropenia (40%) and mucositis (43%) were the most frequent grade 3-4 adverse events. Mean dose of IMRT was 68.8 Gy. Worst late toxicity was xerostomia. Complete response rate was 93%. At 35 months, two patients had locoregional recurrence, three had distant metastases, and one had both. Three-year progression-free survival and overall survival were 79% [95% confidence interval (CI) 64% to 94%] and 87% (95% CI 74%- to 100%), respectively. CONCLUSIONS: In this high-stage nonendemic cancer population, TPF followed by high-dose cisplatin IMRT was promising; this treatment approach deserves evaluation in randomized trials.

Fricke gel-layer dosimetry in high dose-rate brachytherapy.

The aim of this study was to evaluate the reliability of Fricke gel-layer dosimeters for the measurement of in-phantom dose distributions produced by a ((192))Ir brachytherapy source. The doses obtained were compared to measurements performed with thermoluminescent dosimeters and treatment planning calculations. Fricke gel-layer dosimeters have proven to be a promising tool to measure three-dimensional dose distributions in high dose-rate brachytherapy.

FEC (5-fluorouracil, epidoxorubicin and cyclophosphamide) versus EM (epidoxorubicin and mitomycin-C) with or without lonidamine as first-line treatment for advanced breast cancer. A multicentric randomised study. Final results.

From May 1991 to December 1996, 326 patients with advanced metastatic breast cancer were enrolled in a multicentre, randomised, phase III clinical trial with four arms. Patients were randomised to receive chemotherapy according to the FEC regimen (5-fluorouracil (5-FU) 500 mg/m2, epidoxorubicin (EPI) 75 mg/m2 and cyclophosphamide (CFA) 500 mg/m2, intravenously (i.v.). every 3 weeks) or the EM regimen (EPI 75 mg/m2, i.v. every 3 weeks; mitomycin C (MMC) 10 mg/m2, i.v. every 6 weeks) or the same regimens with the addition of lonidamine (LND) until disease progression (orally, thrice daily, 150+150+300 mg); a maximum of eight chemotherapy cycles were planned. The aim of the trial was 2-fold: to compare the EM regimen with the commonly used FEC regimen and to evaluate the possible role of the addition of LND. Patients were eligible if they had histologically proven breast carcinoma, metastatic or locoregional relapse with measurable and/or evaluable disease and were aged between 18 and 70 years: 318 patients were considered eligible. Patients with previous anthracycline-based adjuvant chemotherapy or those who relapsed within 6 months after any adjuvant chemotherapy regimen were excluded. Chemotherapy-related toxicity of grade > or = 3 was manageable and there was no significant difference between the arms in terms of haematological side-effects. The impact on heart function was mild. No increased toxicity was observed in the LND arms (apart from myalgias in 27-30% of the cases). A significant increase in the complete response rate was observed for the FEC/EM + LND group (20.4%) versus the FEC/EM group (10.8%). The median survival time and the median time to progression for the overall series were 608 days and 273 days, respectively; EM+/-LND achieved significantly improved survival and time to progression versus FEC+/-LND (P=0.01). This result was confirmed also when the analysis was restricted to patients previously treated with adjuvant CMF schedules. On the basis of these results, we conclude that EM may represent a valuable alternative to FEC for patients requiring a first-line regimen for advanced/ metastatic breast carcinoma, especially in patients previously treated with CMF in an adjuvant setting. Furthermore, we conclude that, in spite of a better complete response rate in the LND arms, as there was no clear advantage in time to progression or survival resulting from the addition of LND to the FEC or EM regimens, the routine use of LND is not warranted outside a clinical trial.

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

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

Randomized trials on altered fractionation in head and neck cancer radiotherapy with conventional fractionation as control arm: another lap to go.

The Authors present a review of randomized trials on non conventional fractionation in head and neck cancer radiotherapy with conventional fractionation as control arm. Hyperfractionation was studied in 5 trials, accelerated hyperfractionation in 4 trials and accelerated fractionation in 3 trials. Furthermore, the reviews of eminent Authors dealing with the above mentioned trials are summarized. In spite of improved local control rate reported with hyperfractionation, non conventional radiotherapy schedules are not yet recommended as routine clinical practice, but all the radiation oncologists are Invited to join trials on this subject.

Vitamin D receptor gene polymorphism is associated with metastatic breast cancer.

The vitamin D receptor (VDR) has been detected in breast tumor cells. We tested the hypothesis that VDR gene polymorphism might influence the outcome of women affected by breast cancer. A total of 88 breast cancer patients were recruited: 50 women were affected by newly diagnosed breast cancer whereas 38 women suffered from relapsing disease. The individual genetic pattern for VDR was evaluated by DNA extraction followed by PCR amplification of the VDR gene, and digestion with the restriction enzyme BsmI. In 167 healthy women, participating in the osteoporosis prevention trial and being used as a control, we detected 121 Bb heterozygotes (72%), 26 homozygotes for the bb alleles (16%), and 20 homozygotes for the BB alleles (12%). In the newly diagnosed breast cancer group the occurrence of Bb patients was 58% (29/50); bb patients represented 22% (11/50), and BB cases were 20% (10/50). The VDR frequency distribution in the control and primary disease patient groups was not statistically different. In the metastatic cancer group, the prevalence of the bb genotype (14/38; 37%) was double the percentage of control subjects, whereas the percentage of BB women with metastases was half the control group (2/38; 5%). Women who were homozygous bb appeared to have almost a four times higher risk of developing metastases than BB women. Whatever the molecular mechanisms underlying the VDR effects in cancer cells, we believe that the VDR gene polymorphism may represent an important determinant in the evaluation of women affected by breast cancer and might help design targeted therapy.

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

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

Hyperfractionated and accelerated radiation therapy in central nervous system tumors (malignant gliomas, pediatric tumors, and brain metastases).

The authors review the main contributions of the international literature concerning the role of hyperfractionation (HF), accelerated fractionation (AF), and accelerated hyperfractionation (AHF) of the dose in radiation therapy (RT) of central nervous system tumors. Basic rationales, clinical results, acute/late toxicity, and current prospectives are summarized in three sections focusing on malignant gliomas, pediatric brainstem tumors, and brain metastases. In supratentorial malignant gliomas the superiority of AHF (0.89 Gy x 3 fractions/day; total dose 61.4 Gy) over conventional fractionation ((CF) total dose 58 Gy) was demonstrated by a randomized trial. However, the gain in median survival time was less than 6 months. No other randomized trials support the preferential choice of non-CF schedules outside clinical trials. Ongoing trials are exploring the role of AHF in combination with chemotherapy, hypoxic cell and radiosensitizing agents. As for pediatric brainstem tumors, there are no data to support the routine use of HF that should be preferably used in an investigative setting. As late sequelae have been reported in the few long-term survivors, patients should be carefully selected. Regarding brain metastases AF RT and AHF RT, with their faster treatment course, may represent a convenient alternative to CF RT for the palliation of brain metastases. In carefully selected patients with solitary brain metastases non-CF RT may be part of aggressive treatment approaches.

Nonstandard fractionation schedules in radiation therapy of head and neck cancer: a review.

The authors present an updated review of the clinical trials on hyperfractionated and accelerated fractionation schedules in radiotherapy of head and neck cancer. The available results in terms of survival and local control, and acute and late toxicity data are summarized in order to show the current status of this research field. The new breed of fractionation schedules that are on study, designed on the ground of new rationales, are presented as well. Finally, an introductory overview of combination therapy including non standard fractionation radiotherapy associated with chemotherapy is reported.

Staging and follow-up of nasopharyngeal carcinoma: magnetic resonance imaging versus computerized tomography.

PURPOSE: To compare computerized tomography (CT) and magnetic resonance (MR) in relation to their accuracy in the staging of nasopharyngeal carcinoma (NPC); to compare CT and MR in postirradiation follow-up of NPC. METHODS AND MATERIALS: Staging: From 1985 to 1993, 53 patients affected with NPC were studied with MR and CT. All cases were biopsy-proved epithelial carcinoma. Plain and contrast-enhanced CT scans were performed with third-generation scanners. Magnetic resonance were obtained with 0.5 and 1.5 Tesla units in sagittal, axial, and coronal planes. Computerized tomography was chosen as reference method and findings obtained with MR were compared to those obtained with CT. FOLLOW-UP: From 1985 to 1993, 53 patients irradiated with radical intent were followed up with both CT and MR; 71 examinations were performed in all. The baseline follow-up scan was performed, in general, no sooner than 2 months after the end of radiotherapy. All patients were submitted to unlimited clinical follow-up. RESULTS: Staging: Magnetic resonance showed retropharyngeal adenopathies in 6 of 14 cases in which oropharyngeal involvement had been reported after CT; in 3 other patients, adenopathies were recognized on MR, while primary extent to parapharyngeal space had been diagnosed on CT initially. Infiltration of long muscles of the neck was revealed with MR in 14 cases. On the other hand, CT showed bone invasion in 12 patients vs. 8 on MR. Upstaging to T4 occurred in four cases on the basis of CT; no upstaging occurred after MR. FOLLOW-UP: Findings on CT were uncertain in 10 out of 53 patients, disease recurrence was excluded by MR in nine cases, whereas progressive disease was confirmed in one patient. CONCLUSION: Staging: Our series shows that either CT and MR can provide essential information in the staging of NPC. Magnetic resonance, however, seems to provide the most detailed imaging of soft tissue invasion outside the nasopharynx and of retropharyngeal node involvement. Nonetheless, its limitations in evaluating bone details suggest that CT should be always performed when the status of base of skull is uncertain on MR. General reasons and our data indicate that CT can still be considered a valuable tool in routine NPC staging. Follow up: Magnetic resonance may be the modality of choice because it seems to solve, more often than CT, the problems of differentiation between postradiation changes and recurring tumor, apart from those cases showing subtle bone erosions on initial CT scan.

Advanced carcinomas of the oropharynx treated with radiotherapy--a comparison of three different fractionation schemes.

INTRODUCTION: This report reflects a retrospective comparison among historical series of patients with similar site and stage of disease treated by three fractionation schemes. MATERIALS AND METHODS: A hyperfractionation (HF) scheme delivered 1 Gy three times a day, 5 days a week, to a total dose of 60 to 63 Gy over 26 to 29 days. A group of 48 patients received HF. Accelerated fractionation (AF) consists of 2 Gy three times a day, 5 days a week, to a total of 48 to 52 Gy delivered over 11 to 12 days. A group of 46 patients underwent this therapy. A third group of 48 patients were treated with conventional fractionation (CF). These patients received 2 Gy each day, 5 days a week, to a total dose of 60 to 66 Gy. RESULTS: Ned survival at 5 years was 23.8%, 32.8%, and 29.3% for CF, AF, and HF, respectively. The most important cause of failure was inability to control disease at the primary site; however, isolated distant metastasis were observed in 15.4% of all failures. Treatment delays were more common in the HF and CF groups. The highest incidence of late complications occurred in the AF group. CONCLUSIONS: Advanced lesions of the oropharynx have an ominous prognosis. New fractionation regiments represent a warranted approach as an alternative to or an integration into combined chemotherapy and radiotherapy.

Altered fractionation schedules in radiotherapy of head and neck cancer. A review.

The authors review the main contributions of international literature to show the current status in clinical trials on unconventional fractionations of the dose in radiotherapy of head and neck cancers. Several clinical (but only a few randomized) trials have been conducted over the last 15 years using hyperfractionated (HF), accelerated (AF) or mixed (HF-AF) schedules. HF schedules have obtained promising results in terms of local control in comparison with conventional fractionation (CF) of the dose. Improvement in survival was also obtained by the random trials of Pinto and Sanchiz, whereas in EORTC trial no. 22791, the improvement in survival rate was only marginal. A significant increase in local control and, less frequently, in survival has been claimed in several studies using HF-AF. Such data still need to be confirmed by a random study, since EORTC trial 22811 showed superimposable results in comparison with CF. Selection of the most suitable cases for altered fractionation schemes is also being studied in ongoing trials of the EORTC (22851) and RTOG (90-03). As regards acute reactions during and after altered fractionation, they are more severe than after CF. Only pure HF with a dose intensity approximately comparable to CF seems to produce similar acute reactions. Several factors have been found to influence the severity of acute mucosal reactions: interfraction interval, overall treatment time, total dose, and field size. As regards late damage, genuine HF schemes seem to cause roughly equivalent late damage in comparison to CF, whereas high-dose intensity schedules have a higher rate of complications. Interfraction interval, overall treatment time, total dose, fraction size and field size can influence the risk of late sequelae. Before altered fractionations can be considered standard therapy, more data are needed, which should be provided by multicentric randomized trials, some of which are already in progress.

[Follow-up of breast carcinoma]. / Il follow-up del carcinoma mammario.

The rationalization of the follow-up schedule for patients treated for breast cancer appears essential due to the high incidence of this disease. The authors retrospectively analyze their series (3,596 patients, from 1971 to 1990) to assess the patterns of both early loco-regional recurrences and distant metastases. Patterns and outcome of local and regional recurrences are reported according to site. The international literature on the subject is reviewed, and the schedule currently employed in the follow-up of breast cancer patients at the Radiotherapy Unit of Florence is reported. Due to the patterns of relapse a more intensive clinical follow-up schedule is suggested during the first 5 years. Less intensive follow-up continues over the whole patients' life span, since failures can occur even after 5 years. Mammography should be repeated every year in the same period to detect eventual homolateral and/or contralateral relapses. Other diagnostic tools should be employed only when symptoms set in. On the ground of the current literature on the subject, no negative impact on survival should be expected from this follow-up schedule.