Stereotactic ablative radiotherapy for unresectable inferior vena cava tumor thrombus in a patient with renal cell carcinoma: a case report.

PURPOSE: Treatment options for renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVC-TT) are limited and carry substantial risks. Currently, there are no standard treatment options in the setting of recurrent or unresectable RCC with IVC-TT. METHODS: We report our experience of treating an IVC-TT RCC patient with stereotactic body radiation therapy (SBRT). RESULTS: This 62-year-old gentleman presented renal cell carcinoma with IVC-TT and liver metastases. Initial treatment consisted of radical nephrectomy and thrombectomy followed by continuous sunitinib. At 3 months, he developed an unresectable IVC-TT recurrence. A fiducial marker was implanted into the IVC-TT by catheterization. New biopsies were performed at the same time, demonstrating a recurrence of the RCC. SBRT consisted of 5 fractions of 7 Gy to the IVC-TT with excellent initial tolerance. He subsequently received anti-PD1 therapy (nivolumab). At 4 years follow-up, he is doing well with no IVC-TT recurrence and no late toxicity. CONCLUSION: SBRT appears to be a feasible and safe treatment for IVC-TT secondary to RCC in patients who are not candidates for surgery.

Multimodal Management of Locally Advanced Neuroendocrine Cervical Carcinoma: A Single Institution Experience.

OBJECTIVE: The aim of this study was to report our institutional experience of a multimodal approach for treatment of locally advanced high-grade neuroendocrine cervical cancer. METHODS AND MATERIALS: Patients with primary locally advanced neuroendocrine cervical cancer diagnosed between 2001 and 2014 were included. The scheduled treatment sequence was as follows: pelvic +/- para-aortic radiotherapy (according to tumor stage), associated with chemotherapy based on platine-derivate and etoposide regimen, followed with a brachytherapy boost, then completion surgery if there was no progression +/- consolidation etoposide chemotherapy (for a total of 5-6 cycles). Disease-free survival (DFS) and overall survival (OS) were reported and prognostic factors were searched. RESULTS: A total of 24 patients fulfilled inclusion criteria. Median age was 48 (range 22-77 years). Fourteen patients (58%) had pelvic lymph node metastases. After chemoradiation/brachytherapy, a radical hysterectomy could be performed in 18 of 24 patients (75%). Histologically complete resection was achieved in 14 (78%) of 18 patients. Complete pathological response was reported in 7 (39%) of 18. With median follow-up of 29.7 months, 10 (42%) of 24 patients experienced tumor relapse, all associated with distant failure, including one local failure. The DFS and OS rates estimated at 3 years were 55% and 63%, respectively. Lymph node metastases and tumor stage were prognostic for DFS (P = 0.016 and P = 0.022, respectively). Complete resection was associated with a lower incidence of relapses, as compared with microscopically incomplete resection (P = 0.04). A total of 12 (86%) of 14 patients with histologically complete resection were in complete remission at last follow-up. Apart from manageable acute hematological toxicities, most treatment complications were mild to moderate. CONCLUSIONS: This series based on a multimodal management compares favorably with previously published data. Most patients could be eligible to surgery, and complete remission was achieved in 85% of those amenable to complete resection.

Preoperative image-guided brachytherapy in early stage cervical cancers.

OBJECTIVE: To examine the clinical results of a preoperative image-guided pulse-dose-rate brachytherapy (PDR-BT) in early stage cervical cancer. MATERIALS/METHODS: We examined the outcome of consecutive patients with early stage cervical cancer undergoing preoperative image-guided PDR-BT between 2004 and 2013 because of risk factors (lymphovascular embols and/or tumour>2cm). The objective was to deliver 60Gy to 100% of the intermediate risk clinical target volume. Brachytherapy was followed, 6-8weeks later, by a radical hysterectomy/bilateral salpingo-oophorectomy plus pelvic +/- para-aortic lymph node dissection. Patients with positive lymph nodes had postoperative chemoradiation. RESULTS: 77 patients met the above criteria of preoperative PDR-BT. On hysterectomy specimen, 54 (70.1%) presented a complete histological response. Four (5.2%) had a tumour residuum⩾1cm. Median follow-up was 46.8months. 5-Year disease-free survival (DFS) rate was 84.4%. Only one local recurrence was observed. The presence of lymph nodal metastases, a tumour size>3cm and a brachytherapy/surgery time interval⩾9weeks correlated with a poorer DFS. Six postoperative complications were encountered (7.8%). Total reference air kerma correlated with late vaginal toxicity (p=0.02). CONCLUSIONS: A preoperative image-guided PDR-BT was safe and effective. Predictive factors for survival and toxicity were evidenced.

Image-guided adaptive brachytherapy in locally advanced cervical cancer: recent advances and perspectives.

PURPOSE OF REVIEW: Image-guided adaptive brachytherapy (IGABT) is a high-precision radiation that allows defining accurately treatment targets and optimizing their coverage whereas sparing efficiently the surrounding organs at risk. Ten years ago, in a will of harmonizing the reporting of brachytherapy, the Groupe Européen de Curiethérapie - European Society for Radiation Oncology (GEC-ESTRO) published recommendations on target definitions and dosimetric parameters. During the last years, clinical and dosimetric studies supporting their relevance led the International Commission on Radiation Units and Measurements to propose a report on prescribing and reporting. This review aims to highlight the recent advances in IGABT and its future developments. RECENT FINDINGS: Clinical evidence demonstrating the superiority of IGABT over radiographs-based brachytherapy is accumulating. In parallel, dose-volume effects have been established between dose-volume parameters and tumor response or the occurrence of late radiation morbidity. Preliminary studies indicate that planning aims could be adapted to clinical situations and cofactors. The first publications from the large studies led by the GEC-ESTRO enforce these findings. SUMMARY: A trend emerges toward a personalization of treatment with the adaptation of planning aims to prognostic features and the development of individualized applicators. Image-guidance modalities are developed with a better use of MRI or conversely the use of more accessible modalities such as transrectal ultrasound.

Tumor dose-volume response in image-guided adaptive brachytherapy for cervical cancer: A meta-regression analysis.

PURPOSE: Image-guided adaptive brachytherapy is a high precision technique that allows dose escalation and adaptation to tumor response. Two monocentric studies reported continuous dose-volume response relationships, however, burdened by large confidence intervals. The aim was to refine these estimations by performing a meta-regression analysis based on published series. METHODS AND MATERIALS: Eligibility was limited to series reporting dosimetric parameters according to the Groupe Européen de Curiethérapie-European SocieTy for Radiation Oncology recommendations. The local control rates reported at 2-3 years were confronted to the mean D90 clinical target volume (CTV) in 2-Gy equivalent using the probit model. The impact of each series on the relationships was pondered according to the number of patients reported. RESULTS: An exhaustive literature search retrieved 13 series reporting on 1299 patients. D90 high-risk CTV ranged from 70.9 to 93.1 Gy. The probit model showed a significant correlation between the D90 and the probability of achieving local control (p < 0.0001). The D90 associated to a 90% probability of achieving local control was 81.4 Gy (78.3-83.8 Gy). The planning aim of 90 Gy corresponded to a 95.0% probability (92.8-96.3%). For the intermediate-risk CTV, less data were available, with 873 patients from eight institutions. Reported mean D90 intermediate-risk CTV ranged from 61.7 to 69.1 Gy. A significant dose-volume effect was observed (p = 0.009). The D90 of 60 Gy was associated to a 79.4% (60.2-86.0%) local control probability. CONCLUSION: Based on published data from a high number of patients, significant dose-volume effect relationships were confirmed and refined between the D90 of both CTV and the probability of achieving local control. Further studies based on individual data are required to develop nomograms including nondosimetric prognostic criteria.

Sinonasal squamous cell carcinoma without clinical lymph node involvement : Which neck management is best?

OBJECTIVES: The purpose of this work was to report outcomes of patients with nonmetastatic sinonasal squamous cell carcinoma (SNSCC) and to discuss the impact of elective neck irradiation (ENI) and selective neck dissection (SND) in clinically negative lymph node (N0) patients. METHODS: Data from 104 nonmetastatic SNSCC patients treated with curative intent were retrospectively analysed. Uni- and multivariate analyses were used to assess prognostic factors of overall survival (OS) and locoregional control (LRC). RESULTS: Median follow-up was 4.5 years. Eighty-five percent of tumours were stage III-IV. Treatments included induction chemotherapy (52.9 %), surgery (72 %) and radiotherapy (RT; 87 %). The 5­year OS, progression-free survival, and LRC rates were 48, 44 and 57 %, respectively. Absence of surgery predicted a decrease of OS (hazard ratio [HR] 2.6; 95 % confidence interval [CI] 1.4-4.7), and LRC (HR 3.5; 95 % CI 1.8-6.8). Regional relapse was observed in 13/104 (13 %) patients and most common sites were level II (n = 12; 70.6 %), level III (n = 5; 29.4 %) and level Ib (n = 4; 23.5 %). Management of the neck in N0 patients (n = 87) included 11 % SND alone, 32 % ENI alone, 20 % SND + ENI and 37 % no neck treatment. In this population, a better LRC was found according to the management of the neck in favour of SND (94 % vs. 47 %; p = 0.002) but not ENI. CONCLUSION: SND may detect occult cervical positive nodes, allowing selective postoperative RT. ENI (ipsilateral level II, ±Ib and III or bilateral) needs to be proposed in selected patients, especially when SND has not been performed.

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 of treatment time and dose escalation on local control in locally advanced cervical cancer treated by chemoradiation and image-guided pulsed-dose rate adaptive brachytherapy.

PURPOSE: To report the prognostic factors for local control in patients treated for locally advanced cervical cancer with image guided pulsed-dose rate brachytherapy. MATERIALS/METHODS: Patients treated with curative intent by a combination of external beam radiotherapy and pulsed-dose rate brachytherapy were selected. Local failure was defined as any relapse in the cervix, vagina, parametria, or uterus during follow-up. Prognostic factors were selected based on log rank tests and then analyzed with a Cox model. Dose/effect correlations were performed using the probit model. RESULTS: Two hundred and twenty-five patients treated from 2006 to 2011 were included. According to the FIGO classification, 29% were stage IB, 58% stage II, 10% stage III, and 3% stage IVA; 95% received concomitant chemotherapy. Thirty patients were considered having incomplete response or local failure. Among the selected parameters, D90 for HR-CTV, D90 for IR-CTV, the overall treatment time, the TRAK, and the HR-CTV volume appeared significantly correlated with local control in univariate analysis. In multivariate analysis, overall treatment time >55days and HR-CTV volume >30cm(3) appeared as independent. The probit analysis showed significant correlations between the D90 for both CTVs, and the probability of achieving local control (p=0.008 and 0.024). The thresholds to reach to warrant a probability of 90% of local control were 85Gy to the D90 of the HR-CTV and 75Gy to 90% of the IR-CTV (in 2Gy equivalent, α/ß=10). To warrant the same local control rate, the D90 HR-CTV should be significantly increased in stage III-IV tumors, in case of HR-CTV >30cm(3), excessive treatment time, or tumor width at diagnosis >5cm (97, 92, 105, and 92Gy respectively). CONCLUSIONS: Overall treatment time and HR-CTV volume were independent prognostic factors for local control. The D90 for HR and IR CTV were significantly correlated with local control, and D90 HR-CTV should be adapted to clinical criteria.