Combined concomitant boost radiotherapy and chemotherapy in stage III-IV head and neck carcinomas: A comparison of toxicity and treatment results with those observed after radiotherapy alone

Background Alteration of radiation therapy (RT) fractionation and the combination of chemotherapy (CT) with RT represent two predominant fields of current research in the treatment of head and neck carcinomas. To assess the potential integration of these two fields, a retrospective comparison of toxicity and treatment outcome was carried out in stage III-IV patients treated with a concomitant boost RT schedule with or without CT. Patients and methods Fifty-two patients were treated by RT alone and 35 by RT and CT. In the RT group, there were significantly fewer T3-4 tumors (56% vs. 88%, P=0.002) and higher proportion of planned neck dissections (35% vs. 14%, P=0.047). The planned total dose was 69.9 Gy delivered over 5.5 weeks. In 10 cases CT was given before RT and in 25 concomitantly with RT, either alone or with neoadjuvant and/or adjuvant CT. All patients but two had cisplatin-based (CDDP, 100 mg/m2) CT, associated in 28 patients with 5-fluorouracil (5-FU, 1000 mg/m2/24 h × 5). The median follow-up for the surviving patients was 21 and 31 months for the RT and RT-CT groups respectively. Results Grade 3-4 acute toxicity (RTOG) was observed in 73% and 86% of patients, and grade 3 dysphagia in 31% and 57% (P=0.02) respectively in the RT and RT-CT groups. The rates of grade 3-4 late complications were similar in the two groups (5% vs. 12%). At three years, actuarial loco-regional control (LRC) was 57% and 66% (P%0.66) and overall survival was 56% and 47% (P=0.99) in the RT and RT-CT groups respectively. Conclusion While acute toxicity was higher compared with RT alone, this accelerated RT schedule was feasible in association with 5-FU/CDDP, even administered concomitantly. Despite the significant proportion of more advanced disease in the RT-CT group, LRC was similar to that obtained by RT alone. Combinations of concomitant boost RT and chemotherapy merit further investigation in prospective trial

Prognostic value of cerebrospinal fluid cytology in pediatric medulloblastoma

Background: Although the demonstration of leptomeningeal dissemination is the most important predictor of poor outcome in children with medulloblastoma, there is lack of consensus on the prognostic value of a positive cerebrospinal fluid (CSF) cytology (i.e., stage M1). Patients and methods: Eighty-six pediatric medulloblastoma patients treated in Switzerland between 1972-1991 were retrospectively studied regarding the influence of M-stage on prognosis. 39 were M0, 13 M1, 15 Mx, 17 M2, and 2 M3. Results: Five- and 10-year overall survival rates were 76% and 54% for M0, 68% and 50% for Mx, 36% and 25% for M1, and 22% and 22% for M2-3 (P < 0.001), respectively. No significant survival differences were observed between M1 and M2-3 patients. Among 26 patients with only postoperative CSF cytologies, seven were positive. Their outcome was similar to that of six preoperatively staged M1 and significantly different from that of M0 patients (P = 0.001). In 14 patients both pre- and postoperative CSF cytology was performed. Total agreement was observed between the pre- and postoperative results (six positive and eight negative). Among the 19 M2-3 patients CSF cytology was positive in eight, negative in five, and unknown in six. Conclusions: A positive CSF cytology either pre- or post-operatively predicts for a poor outcome, similar to that observed in stage M2-3 patients. A postoperative cytology is likely to be concordant with cytologic results obtained preoperatively, and seems to have the same prognostic significance. A negative cytology, however, does not exclude a more advanced stag

Excess of cardiovascular mortality among node-negative breast cancer patients irradiated for inner-quadrant tumors

Background: Radiotherapy of the left breast is associated with higher cardiovascular mortality linked to cardiotoxic effect of irradiation. Radiotherapy of inner quadrants can be associated with greater heart irradiation, but no study has evaluated the effect of inner-quadrant irradiation on cardiovascular mortality. Patients and methods: We identified 1245 women, the majority with breast-conserving surgery, irradiated for primary node-negative breast cancer from 1980 to 2004 registered at the Geneva Cancer Registry. We compared breast cancer-specific and cardiovascular mortality between inner-quadrant (n = 393) versus outer-quadrant tumors (n = 852) by multivariate Cox regression analysis. Results: After a mean follow-up of 7.7 years, 28 women died of cardiovascular disease and 91 of breast cancer. Patients with inner-quadrant tumors had a more than doubled risk of cardiovascular mortality compared with patients with outer-quadrant tumors (adjusted hazard ratio 2.5; 95% confidence interval 1.1-5.4). Risk was particularly increased in the period with higher boost irradiation. Patients with left-sided breast cancer had no excess of cardiovascular mortality compared with patients with right-sided tumors. Conclusions: Radiotherapy of inner-quadrant breast cancer is associated with an important increase of cardiovascular mortality, a possible result of higher irradiation of the heart. For patients with inner-quadrant tumors, the heart should be radioprotecte

Once-a-week or every-other-day urethra-sparing prostate cancer stereotactic body radiotherapy, a randomized phase II trial: 18 months follow-up results

Background To present the 18 months results from a prospective multicenter phase II randomized trial of short vs protracted urethra-sparing stereotactic body radiotherapy (SBRT) for localized prostate cancer (PCa).Methods Between 2012 and 2015, a total of 170 PCa patients were randomized to 36.25 Gy in 5 fractions (6.5 Gy x 5 to the urethra) delivered either every other day (EOD, arm A, n = 84) or once a week (QW, arm B, n = 86). Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v4.0 scale), IPSS, and QoL scores were assessed at baseline, at the 5th fraction (5fx), 12th weeks (12W), and every 6 months after SBRT. The primary endpoint was biochemical control at 18 months and grade >= 3 toxicity (including grade >= 2 for urinary obstruction/retention) during the first 3 months.Results Among the 165 patients analyzed, the toxicity stopping rule was never activated during the acute phase. Maximum acute grade 2 GU toxicity rates at 5fx were 17% and 19% for arms A and B, respectively, with only 2 cases of grade 2 GI toxicity at 5fx in arm A. At month 18, grade >= 2 GU and GI toxicity decreased below 5% and 2% for both arms. No changes in EORTC QLQ-PR25 scores for GU, GI, and sexual domains were observed in both arms between baseline and month 18. Four biochemical failures were observed, 2 in each arm, rejecting the null hypothesis of an unfavorable response rate = 95% rate.Conclusions At 18 months, urethra-sparing SBRT showed a low toxicity profile, with minimal impact on QoL and favorable biochemical control rates, regardless of overall treatment time (EOD vs QW)

First in-human radiation dosimetry of the gastrin-releasing peptide (GRP) receptor antagonist (68)Ga-NODAGA-MJ9.

Gastrin-releasing peptide receptor antagonists have promise in theranostics of several highly incident tumours, including prostate and breast. This study presents the first human dosimetry of &lt;sup&gt;68&lt;/sup&gt; Ga-NODAGA-MJ9 in the first five consecutive patients with recurrent prostate cancer included in a dual-tracer positron emission tomography (PET) protocol. Five male patients with biochemical relapse of prostate adenocarcinoma underwent four whole-body time-of-flight PET/CT scans within 2 h after tracer injection. To be used as input in OLINDA/EXM 2.0, time-integrated activity coefficients were derived from manually drawn regions of interest over the following body regions: brain, thyroid, lungs, heart, liver, gallbladder, spleen, stomach, kidneys, adrenals, red marrow, pancreas, intestines, urinary bladder and whole body. Organ absorbed doses and effective dose (ED) were calculated with OLINDA/EXM 2.0 using the NURBS voxelized phantoms adjusted to the ICRP-89 organ masses and ICRP103 tissue-weighting factors. Additional absorbed dose estimations were performed with OLINDA/EXM 1.1 to be comparable with similar previous publications. The body regions receiving the highest absorbed doses were the pancreas, the urinary bladder wall, the small intestine and the kidneys (260, 69.8, 38.8 and 34.8 μGy/MBq respectively). The ED considering a 30-min urinary voiding cycle was 17.6 μSv/MBq in male patients. The increment of voiding time interval produced a significant increase of absorbed doses in bladder, prostate and testes, as well as an increase of ED. ED also increased if calculated with OLINDA/EXM 1.1. These results have been discussed in view of similar publications on bombesin analogues or on other commonly used theranostic peptides. The pancreas is the most irradiated organ after the injection of &lt;sup&gt;68&lt;/sup&gt; Ga-NODAGA-MJ9, followed by the urinary bladder wall, the small intestine and the kidneys. ED is in the same range of other common &lt;sup&gt;68&lt;/sup&gt; Ga-labelled peptides. Differences with similarly published studies on bombesin analogues exist, and are mainly dependent on the methodology used for absorbed dose calculations. Clinicaltrial.Gov identifier: NCT02111954 , posted on 11/042014

Prognostic value of cerebrospinal fluid cytology in pediatric medulloblastoma. Swiss Pediatric Oncology Group

BACKGROUND: Although the demonstration of leptomeningeal dissemination is the most important predictor of poor outcome in children with medulloblastoma, there is lack of consensus on the prognostic value of a positive cerebrospinal fluid (CSF) cytology (i.e., stage M1). PATIENTS AND METHODS: Eighty-six pediatric medulloblastoma patients treated in Switzerland between 1972-1991 were retrospectively studied regarding the influence of M-stage on prognosis. 39 were M0, 13 M1, 15 Mx, 17 M2, and 2 M3. RESULTS: Five- and 10-year overall survival rates were 76% and 54% for M0, 68% and 50% for Mx, 36% and 25% for M1, and 22% and 22% for M2-3 (P &lt; 0.001), respectively. No significant survival differences were observed between M1 and M2-3 patients. Among 26 patients with only postoperative CSF cytologies, seven were positive. Their outcome was similar to that of six preoperatively staged M1 and significantly different from that of M0 patients (P = 0.001). In 14 patients both pre- and postoperative CSF cytology was performed. Total agreement was observed between the pre- and postoperative results (six positive and eight negative). Among the 19 M2-3 patients CSF cytology was positive in eight, negative in five, and unknown in six. CONCLUSIONS: A positive CSF cytology either pre- or postoperatively predicts for a poor outcome, similar to that observed in stage M2-3 patients. A postoperative cytology is likely to be concordant with cytologic results obtained preoperatively, and seems to have the same prognostic significance. A negative cytology, however, does not exclude a more advanced stage

Oral mucositis and selective elimination of oral flora in head and neck cancer patients receiving radiotherapy: a double-blind randomised clinical trial

Mucositis is an acute inflammation of the oral mucosa because of radiotherapy and/or chemotherapy. All patients receiving radiotherapy in the head and neck region develop oral mucositis. The aim of this study was to analyse the effects of selective oral flora elimination on radiotherapy-induced oral mucositis, in a double-blind, randomised, placebo-controlled trial. Sixty-five patients with a malignant tumour in the head and neck regions to be treated with primary curative or postoperative radiotherapy participated in this study. The patients received either the active lozenges of 1 g containing polymyxin E 2 mg, tobramycin 1.8 mg and amphotericin B 10 mg (PTA) (33 patients) or the placebo lozenges (32 patients), four times daily during the full course of radiotherapy. Mucositis, changes in the oral flora, quality of feeding and changes of total body weight were assessed. Mucositis score did not differ between the groups during the first 5 weeks of radiotherapy. Nasogastric tube feeding was needed in six patients (19%) of the placebo group and two patients (6%) of the PTA group (P=0.08). Mean weight loss after 5 weeks of radiation was less in the PTA group (1.3 kg) (s.d.: 3.0) than in the placebo group (2.8 kg) (s.d.: 2.9) (P=0.05). Colonisation index of Candida species and Gram-negative bacilli was reduced in the PTA group and not in the placebo group (P<0.05). No effect on other microorganisms was detected. In conclusion, selective oral flora elimination in head and neck irradiation patients does not prevent the development of severe mucositis. Record 8 of 10 - SilverPlatter MEDLINE(R)

Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic astrocytoma: validation of Radiation Therapy Oncology Group-Recursive Partitioning Analysis in the IMRT and temozolomide era

Since the development of the Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) risk classes for high-grade glioma, radiation therapy in combination with temozolomide (TMZ) has become standard care. While this combination has improved survival, the prognosis remains poor in the majority of patients. Therefore, strong interest in high-grade gliomas from basic research to clinical trials persists. We sought to evaluate whether the current RTOG-RPA retains prognostic significance in the TMZ era or alternatively, if modifications better prognosticate the optimal selection of patients with similar baseline prognosis for future clinical protocols. The records of 159 patients with newly-diagnosed glioblastoma (GBM, WHO grade IV) or anaplastic astrocytoma (AA, WHO grade III) were reviewed. Patients were treated with intensity-modulated radiation therapy (IMRT) and concurrent followed by adjuvant TMZ (n = 154) or adjuvant TMZ only (n = 5). The primary endpoint was overall survival. Three separate analyses were performed: (1) application of RTOG-RPA to the study cohort and calculation of subsequent survival curves, (2) fit a new tree model with the same predictors in RTOG-RPA, and (3) fit a new tree model with an expanded predictor set. All analyses used a regression tree analysis with a survival outcome fit to formulate new risk classes. Overall median survival was 14.9 months. Using the RTOG-RPA, the six classes retained their relative prognostic significance and overall ordering, with the corresponding survival distributions significantly different from each other (P < 0.01, χ2 statistic = 70). New recursive partitioning limited to the predictors in RTOG-RPA defined four risk groups based on Karnofsky Performance Status (KPS), histology, age, length of neurologic symptoms, and mental status. Analysis across the expanded predictors defined six risk classes, including the same five variables plus tumor location, tobacco use, and hospitalization during radiation therapy. Patients with excellent functional status, AA, and frontal lobe tumors had the best prognosis. For patients with newly-diagnosed high-grade gliomas, RTOG-RPA classes retained prognostic significance in patients treated with TMZ and IMRT. In contrast to RTOG-RPA, in our modified RPA model, KPS rather than age represented the initial split. New recursive partitioning identified potential modifications to RTOG-RPA that should be further explored with a larger data set