Kim Cao

Clinical outcomes of definitive chemoradiation followed by intracavitary pulsed-dose rate image-guided adaptive brachytherapy in locally advanced cervical cancer

OBJECTIVE To report the outcomes and late toxicities of patients with locally advanced cervical cancer treated with concomitant chemoradiation (CRT) followed by intracavitary image-guided adaptive brachytherapy (IGABT). METHODS Data from consecutive patients with histologically proven stage IB-IVA cervical cancer treated with curative intent in a single institution were analyzed. After pelvic +/- para-aortic external-beam radiation therapy, they received pulsed-dose rate IGABT following GEC-ESTRO recommendations. RESULTS Two hundred and twenty-five patients were enrolled. Sixty-five percent were stage≥IIB according to FIGO classification. Ninety-five percent received CRT. Mean D90 to HR and IR-CTV were 80.4+/-10.3Gy and 67.7+/-6.1Gy. After a median follow-up of 38.8months, 3-year local control and overall survival rates were 86.4% and 76.1%, respectively. A trend for a detrimental effect of tumor stage on local control rates was observed with 3-year local control rates of 100% for stages IB1 and IIA, 90.5 for IB2, 85.8% for IIB, 50% for IIIA, 77.1 for IIIB, and 66.7% for IVA tumors (p=0.06). Local control rates at 3years were 95.6% in the group of patients with D90 of HR-CTV≥85Gy, 88.8% in those with D90 between 80 and 85Gy, and 80% when D90<80Gy (p=0.018). Eighteen severe late gastrointestinal and urinary effects affecting 14 patients were reported corresponding with a crude incidence of 6.6%. CONCLUSIONS CRT followed by IGABT provides high local control rates with limited toxicity. Reaching high doses is mandatory to achieve local control and interstitial brachytherapy is necessary in advanced diseases.

Pulsed-dose rate image-guided adaptive brachytherapy in cervical cancer: Dose-volume effect relationships for the rectum and bladder

PURPOSE To establish dose-volume effect correlations for late bladder and rectum side effects in patients treated for locally advanced cervical cancer with concomitant chemoradiation followed by pulsed-dose rate image-guided adaptive brachytherapy. MATERIAL AND METHODS The dosimetric data, converted in 2 Gy equivalent, from 217 patients were confronted to late morbidity defined as any event lasting or occurring 90 days after treatment initiation. Toxicity was assessed using the CTC-AE 3.0. Probit analyses and Log rank tests were performed to assess relationships. RESULTS One hundred and sixty-one urinary and 58 rectal events were reported, affecting 98 (45.1%) and 51 (23.5%) patients, respectively. Cumulative incidences for grade 2-4 bladder and rectal morbidity were 24.3% and 9.6% at 3 years, respectively. Significant relationships were observed between grade 2-4 and 3-4 events and D0.1cm(3) and D2 cm(3) for the bladder and between grade 1-4 and 2-4 event probability and rectal D2 cm(3). The effective doses for 10% grade 2-4 morbidity were 65.3 Gy (59.8-81.3), and 55.4 Gy (15.7-63.6), respectively, for the rectum and bladder. Without considering urinary and rectal incontinence, for which the pertinence of correlating them with D2 cm(3) is questionable, ED10 were 68.5 Gy (62.9-110.6) and 65.5 Gy (51.4-71.6 Gy). When sorting patients according to D2 cm(3) levels, patients with high D2 cm(3) had significantly lower morbidity free survival rates for grade 1-4 and 2-4 urinary and rectal morbidity. CONCLUSION Significant dose-volume effect relationships were demonstrated between the modern dosimetric parameters and the occurrence of late rectal and urinary morbidity in patients treated with pulsed-dose-rate brachytherapy. Further studies are required to refine these relationships according to clinical cofactors, such as comorbidities.

Impact de la radiothérapie sur la fertilité féminine

Radiation therapy may have deleterious effects on female fertility. It can cause ovarian dysfunction, uterine damages or disrupt the hypothalamic-pituitary axis. These effects occur at varying dose levels usually relatively low compared to the prescribed doses. Other co-factors influence the effects of radiation therapy on fertility, such as age or therapy with alkylating agents. This review aims to make an update on the current state of knowledge about the impact of radiotherapy on female fertility.

Outcomes of postoperative radiation therapy for breast cancer in older women according to age and comorbidity status: An observational retrospective study in 752 patients

OBJECTIVES The aim of this study was to assess efficacy, tolerability, and the impact of comorbidities on outcomes in older women treated by radiation therapy (RT) for non-metastatic breast cancer. MATERIALS AND METHODS Women aged ≥70 years at diagnosis who received postoperative RT for primary non-metastatic BC between 2003 and 2009 were retrieved from the Institut Curie registry. We calculated the Charlson Comorbidity Index (CCI) for each patient. We analyzed overall survival (OS), progression free survival (PFS), and acute and late toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. RESULTS A total of 752 patients were included in this study. Median age at diagnosis was 75 years [70-93.3]. With a median follow-up of 7.3 years [0.4-12.9], OS and PFS at 5 years were 87.2% CI95%[84.8-89.8] and 85.7% CI95%[83.1-88.3], respectively. OS at 5 years was statistically different according to the CCI: 90.7% CI95%[87.6-93.9] for a CCI of 0, 85.8% CI95%[81.8-90.1] for a CCI of 1, and 79.1% CI95%[71.1-87.9] for a CCI ≥ 2 (p < 0.01, log-rank test), respectively. Similar results were found for PFS (p < 0.05, log-rank test). Most (23.3%) of the patients had no toxicities; of those who experienced side-effects, the majority were grade I or II (96.9%). CONCLUSION Postoperative RT for non-metastatic BC in older women is effective and well-tolerated. Outcome is impacted by age and comorbidities, which are clear independent prognostic factors.

Pelvic insufficiency fracture (PIF) incidence in patients treated with intensity-modulated radiation therapy (IMRT) for gynaecological or anal cancer: single-institution experience and review of the literature

OBJECTIVE To summarize the results of pelvic insufficiency fracture (PIF) incidence in patients with anal or gynaecological cancer treated by pelvic intensity-modulated radiation therapy (IMRT). METHODS The clinical and morphological (CT and/or pelvic MRI) characteristics of patients treated by IMRT at our institution between 2007 and 2014 were analyzed. The global incidence of PIF after external beam radiotherapy and the impact of tumour site (gynaecological or anal cancer) were determined. A dosimetric study was then performed to compare patients with and without pelvic fracture. RESULTS 341 patients were treated by IMRT for gynaecological or anal cancer between 2007 and 2014. 15 patients experienced at least 1 pelvic fracture after external beam radiotherapy, corresponding to an overall incidence of 4.4%. Age and menopausal status were correlated with an increased fracture risk (p = 0.0274 and p < 0.0001, respectively). The site of the primary tumour (gynaecological or anal canal) was not associated with an excess fracture risk. The median maximum dose received at the fracture site was 50.3 Gy (range: 40.8-68.4 Gy). CONCLUSION The incidence of pelvic fracture after IMRT is low, but is higher after the age of 50 and in patients who are postmenopausal. Pre-treatment evaluation of bone density by bone densitometry and phosphorus-calcium assessment could be useful prior to the management of these patients. Advances in knowledge: Pelvic fractures are a frequent complication after radiotherapy. The influence of IMRT and clinical characteristics were evaluated in this study.

Implantable drug delivery systems should be inserted outside radiation therapy fields in breast cancer patients

http://dx.doi.org/10.1016/j.radonc.2015.04.016 0167-8140/ 2015 Published by Elsevier Ireland Ltd. To the Editor Implantable drug delivery systems (DDS) are extensively used in Oncology. Patients with breast cancer undergo radiation therapy (RT) while chemotherapy is administered. When the patient has positive lymph nodes, the supra-clavicular nodes (SCN) need to be irradiated. This study assesses the dosimetric consequences of the presence of a DDS in an irradiation field as well as the feasibility of inserting the DSS on the contralateral side of the treated breast. There are no published data about the interaction of DDS and breast cancer irradiation. At our Institute, the DDS used (Heliosite , Vygon, Paris, France) include a titanium cylindrical pellet of 8 mm diameter (encased in silicon) in order to prevent injuring the patient when inserting the needle. A clinical workflow was designed so that the physician inserting the DDS (at our Institute, the Anesthetist) was aware of the geometry of RT treatment fields for each patient. When clinically possible, the Anesthetist should insert the DDS on the contralateral side of the treated breast. Gafchromic EBT films were placed between slabs of a solid water phantom, in a direction that was parallel to the direction of the electron or photon beam. The DDS was positioned flat on top of the phantom. Two beam qualities were used: electrons of 12 MeV and photons of 4 MV, as they represent the beam qualities that are mostly used to irradiate supra clavicular nodes. Gafchromic films were scanned with a Vidar scanner and dose profiles were extracted at a depth of 2.7 cm representative of the average clinical depth of SCN. We retrospectively looked at fifty consecutive breast patients with 24 left side breast cancers. In 100% of cases the implantable port was inserted on the opposite side of the treated breast: 24 were placed on the right side of the patient, and 24 on the left side. There were 2 cases of bilateral breast cancers, of them only one with supra-clavicular RT fields. In her case the implantable port was placed at distance from the upper field border. Film measurements have shown that the DDS provoked an under dosage of up to 45% of the prescribed dose with electrons and up to 15% with photons due to the presence of titanium in the device. Moreover the dose distribution underneath the DDS was very inhomogeneous. Positioning the DDS on the opposite side of the radiation fields when clinically possible is feasible and is recommended. It was possible to design a workflow that allowed the anesthetist or surgeon to anticipate on which side the port should be implanted and discussion with the radiation oncologist is needed before the procedure. For the clinical cases where the DDS could not be placed outside the treated areas, dosimetric considerations must be given: the use of electrons should be avoided and a special care should be given to treatment planning to compensate for under dosage.

SynthèseImpact de la radiothérapie sur la fertilité féminineImpact of radiotherapy on female fertility

Radiation therapy may have deleterious effects on female fertility. It can cause ovarian dysfunction, uterine damages or disrupt the hypothalamic-pituitary axis. These effects occur at varying dose levels usually relatively low compared to the prescribed doses. Other co-factors influence the effects of radiation therapy on fertility, such as age or therapy with alkylating agents. This review aims to make an update on the current state of knowledge about the impact of radiotherapy on female fertility.

Impact of radiotherapy on female fertility

Radiation therapy may have deleterious effects on female fertility. It can cause ovarian dysfunction, uterine damages or disrupt the hypothalamic-pituitary axis. These effects occur at varying dose levels usually relatively low compared to the prescribed doses. Other co-factors influence the effects of radiation therapy on fertility, such as age or therapy with alkylating agents. This review aims to make an update on the current state of knowledge about the impact of radiotherapy on female fertility.