Brachytherapy quality assurance in the PORTEC-4a trial for molecular-integrated risk profile guided adjuvant treatment of endometrial cancer.

OBJECTIVE: The PORTEC-4a trial investigates molecular-integrated risk profile guided adjuvant treatment for endometrial cancer. The quality assurance programme included a dummy run for vaginal brachytherapy prior to site activation, and annual quality assurance to verify protocol adherence. Aims of this study were to evaluate vaginal brachytherapy quality and protocol adherence. METHODS: For the dummy run, institutes were invited to create a brachytherapy plan on a provided CT-scan with the applicator in situ. For annual quality assurance, institutes provided data of one randomly selected brachytherapy case. A brachytherapy panel reviewed and scored the brachytherapy plans according to a checklist. RESULTS: At the dummy run, 15 out of 21 (71.4%) institutes needed adjustments of delineation or planning. After adjustments, the mean dose at the vaginal apex (protocol: 100%; 7 Gy) decreased from 100.7% to 99.9% and range and standard deviation (SD) narrowed from 83.6-135.1 to 96.4-101.4 and 8.8 to 1.1, respectively. At annual quality assurance, 22 out of 27 (81.5%) cases had no or minor and 5 out of 27 (18.5%) major deviations. Most deviations were related to delineation, mean dose at the vaginal apex (98.0%, 74.7-114.2, SD 7.6) or reference volume length. CONCLUSIONS: Most feedback during the brachytherapy quality assurance procedure of the PORTEC-4a trial was related to delineation, dose at the vaginal apex and the reference volume length. Annual quality assurance is essential to promote protocol compliance, ensuring high quality vaginal brachytherapy in all participating institutes.

Incorporating PARP-inhibitors into clinical routine: A tailored treatment strategy to tackle ovarian cancer.

DNA repair mechanisms play a key role in oncogenesis and cancer progression in women with BRCA mutation-positive (BRCAm) ovarian cancer (OC). The BRCA1/2 and poly(ADP-ribose) polymerase (PARP) proteins are considered the foremost mediators among the various components of double-strand and single-strand repair, respectively. A series of new therapeutic drugs that target PARP have been developed for BRCAm OC. This class of agents provokes tumour-specific cytotoxicity with minimal side effects by inducing synthetic lethality, of which they are the first clinical example. The European Medicines Agency granted accelerated licensing approval for the first-in-class-drug that inhibits PARP, olaparib (Lynparza™, AstraZeneca). Olaparib can be used as a monotherapeutic maintenance treatment in patients with platinum-sensitive relapsed (germline and/or somatic) BRCAm high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer responsive to platinum-based chemotherapy. Seen in light of these recent events, this review article will focus on (a) how PARP-inhibitors exploit cancer-specific defects in the homologous recombination repair apparatus and (b) how BRCA testing is implemented in routine clinical care.

Whole abdominopelvic radiotherapy in the palliative treatment of pseudomyxoma peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare clinical syndrome characterized by mucinous peritoneal disease arising from disseminated peritoneal adenomucinosis. Primary treatment involves a combination of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). There is no consensus on the proper treatment of recurrent PMP. In selected patients, repeated cytoreductive surgery with or without HIPEC might improve outcome. However, every repeated debulking procedure becomes less effective with increased morbidity. CASE REPORT: We present a case of a patient with intestinal obstruction caused by recurrent pseudomyxoma peritonei. We treated the patient with whole abdominopelvic radiotherapy (WAPRT) using intensity-modulated arc therapy (IMAT) to a total dose of 33 Gy, delivered in 22 daily fractions. The treatment was well tolerated and resulted in resolution of the obstruction for a period of 24 months. CONCLUSION: To the best of our knowledge, we present the first case report showing the possibility of resolving intestinal obstruction with WAPRT in a patient with recurrent PMP. It is our opinion that WAPRT delivered by IMAT, in analogy with ovarian cancer, should be considered as a palliative treatment option in managing patients with recurrent PMP especially in case of obstruction.

Radiation-induced oesophagitis in lung cancer patients. Is susceptibility for neutropenia a risk factor?

BACKGROUND: Radiation-induced oesophagitis is a major side effect of concurrent chemotherapy and radiotherapy. A strong association between neutropenia and oesophagitis was previously shown, but external validation and further elucidation of the possible mechanisms are lacking. METHODS AND PATIENTS: A total of 119 patients were included at two institutions. The concurrent group comprised 34 SCLC patients treated with concurrent carboplatin and etoposide, and concurrent chest irradiation, and 36 NSCLC patients with concurrent cisplatin and etoposide, and concurrent radiotherapy, while the sequential group comprised 49 NSCLC patients received sequential cisplatin and gemcitabine, and radiotherapy. RESULTS: Severe neutropenia was very frequent during concurrent chemoradiation (grade: 4 41.4%) and during induction chemotherapy in sequentially treated patients (grade 4: 30.6%), but not during radiotherapy (only 4% grade 1). In the concurrent group, the odds ratios of grade 3 oesophagitis vs. neutropenia were the following: grade 2 vs. grade 0/1: 5.60 (95% CI 1.55-20.26), p = 0.009; grade 3 vs. grade 0/1: 10.40 (95% CI 3.19-33.95); p = 0.0001; grade 4 vs. grade 0/1: 12.60 (95% CI 4.36-36.43); p < 0.00001. There was no correlation between the occurrence of neutropenia during induction chemotherapy and acute oesophagitis during or after radiotherapy alone. In the univariate analysis, total radiation dose (p < 0.001), overall treatment time of radiotherapy (p < 0.001), mean oesophageal dose (p = 0.038) and neutropenia (p < 0.001) were significantly associated with the development of oesophagitis. In a multivariate analysis, only neutropenia remained significant (p = 0.023). CONCLUSION: We confirm that neutropenia is independently correlated with oesophagitis in concurrent chemoradiation, but that the susceptibility for chemotherapy-induced neutropenia is not associated with radiation-induced oesophagitis. Further studies focusing on the underlying mechanisms are thus warranted.

Intensity-modulated arc therapy with cisplatin as neo-adjuvant treatment for primary irresectable cervical cancer. Toxicity, tumour response and outcome.

PURPOSE: The goal of this work was to evaluate the feasibility and outcome of intensity-modulated arc therapy ± cisplatin (IMAT ± C) followed by hysterectomy for locally advanced cervical cancer. PATIENTS AND METHODS: A total of 30 patients were included in the study. The primary tumour and PET-positive lymph node(s) received a simultaneous integrated boost. Four weeks after IMAT ± C treatment, response was evaluated. Resection consisted of hysterectomy with or without lymphadenectomy. Tumour response, acute and late radiation toxicity, postoperative morbidity and outcome were evaluated. RESULTS: All hysterectomy specimens were macroscopically tumour-free with negative resection margins; pathological complete response was 40%. In 2 patients, one resected lymph node was positive. There was no excess in postoperative morbidity. Apart from two grade 3 hematologic toxicities, no grade 3 or 4 acute radiation toxicity was observed. No grade 3, 1 grade 4 (4%) intestinal, and 4 grade 3 (14%) urinary late toxicities were observed. The 2-year local and regional control rates were 96% and 100%, respectively. The 2-year distant control rate was 92%. Actuarial 2-year progression free survival rate was 89%. Actuarial 1- and 2-year overall survival rates were 96% and 91%, while 3-year overall survival was 84%. CONCLUSION: Surgery after IMAT ± C is feasible with low postoperative morbidity and radiation toxicity. Local, regional, distant control and survival rates are promising.

Identification and quantification of 77 pesticides in groundwater using solid phase coupled to liquid-liquid microextraction and reversed-phase liquid chromatography.

This paper describes a method for the extraction, separation, identification, and quantification of 77 pesticides (neutral, acidic, and basic) including some s-triazine metabolites. The method is appropriate for organically (e.g. with humic acids) highly loaded groundwater samples. A comparative study of a pH-controlled mixed solid phase (LiChroprep RP18/LiChrolut EN) extraction with different desorption solvents (acetonitrile or acetonitrile and dichloromethane/methanol) is elaborated. A subsequent liquid-liquid microextraction reduces matrix effects. The pesticides in the sample are separated using RP-HPLC, detected, and identified by diode array. The efficiency is illustrated on a natural groundwater sample from a phreatic aquifer.