Effects and consequences of Digisonic SP cochlear implant on radiotherapy planning.

The aim of this study was to assess dose attenuation by a Digisonic SP cochlear implant (CI) and evaluate its impact on treatment planning. The Digisonic CI was irradiated with 6 MV photons. Overall dose attenuation was assessed with MOSFET dosimeters and Gafchromic films. In addition, we evaluated the attenuation of separate CI components. Dose attenuation was also calculated using different radiation treatment planning systems (TPS) softwares and dose calculation algorithms. The CI was placed on a head phantom. Single-beam and multiple-beam plans were evaluated for dose attenuation using two radiation techniques (Conformal and Stereotactic radiotherapy) and four different algorithms (Clarkson, Point Kernel-Superposition, Ray Tracing and Monte Carlo). MOSFET and Gafchromics film showed maximal 6-7.5% radiation dose attenuation, at the center of the CI. Computerized TPS-based dose attenuation by the implant was 4-8.1%, using a single ipsilateral field. No clinically meaningful dose attenuation was found in multiple field plans owing to the contribution of various beam paths with only a couple going through the implant using either conventional conformal or stereotactic treatment plans. Dose attenuation induced by a Digisonic SP CI is about 6%, for single 6 MV photon field. This dose reduction is unlikely to be clinically significant, as single-field radiotherapy plans to this anatomic region are uncommon.

Organ or sphincter preservation for rectal cancer. The role of contact X-ray brachytherapy in a monocentric series of 112 patients.

BACKGROUND: Contact X-ray brachytherapy (CXB) has been used at Centre Antoine Lacassagne since 2002 to increase the chance of conservative treatment (organ or sphincter preservation) in rectal cancer. A consecutive series of 112 patients (pts) is reported. METHODS: Three protocols were used in selected rectal adenocarcinomas. Group 1: T1 N0 treated with local excision (LE) followed by adjuvant CXB. Group 2: T2 or 'early' T3 N0 treated with CXB combined with chemoradiotherapy (CRT) followed by surveillance or LE. Group 3: distal 'locally advanced' T3 N0-2 treated with CXB and CRT before total proctectomy. RESULTS: Group 1: 27 pt (pTis: 3; pT1: 21; pT2: 3). After LE with CXB alone (20 pt) or CXB + CRT (7 pt) one local recurrence occurred. Organ preservation was achieved in 26 pt (96%). Group 2: 45 pt (T1: 2; T2: 23; T3: 20) treated with CXB alone (4 pt) or CXB + CRT or external beam radiotherapy (EBRT) (41 pt). A clinical complete response (cCR) was observed in 43/45 (96%) and 3 pt developed a local recurrence (11% at 5 years). The specific survival was 76% at 5 years and the rate of organ preservation was 89% (40/45 pt) with good bowel function in 36 pt. Group 3: 40 pt, anterior resection (with sphincter preservation) was possible in 35 pt (86%) with a 3-year local recurrence of 6%. CONCLUSION: CXB usually combined as a boost with CRT or EBRT may safely increase the chance of a conservative treatment (organ or sphincter preservation) for selected rectal cancers.

Combination of phosphotidylinositol-3-kinase targeting with cetuximab and irradiation: A preclinical study on an orthotopic xenograft model of head and neck cancer.

BACKGROUND: The purpose of this study was to investigate the effects of combining the phosphotidylinositol-3-kinase (PI3K) inhibitor buparlisib (BKM)120 with the anti-epidermal growth factor receptor (EGFR) agent cetuximab and radiotherapy (RT) on an orthotopic model of head and neck squamous cell carcinoma (HNSCC). METHODS: We evaluated the antitumor efficacy of BKM120, cetuximab, and RT, administered alone or in combination, using the human PIK3CA-mutated HNSCC cell line, CAL33, injected into the floor of the mouth of nude mice. RESULTS: Compared with control, the BKM120-cetuximab and the BKM120-cetuximab-RT combinations led to the highest tumor inhibition (p < .001). The highest inhibitory effect of treatments on cell proliferation, mitogen-activated protein kinase (MAPK) and PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathways were found with the BKM120-cetuximab association. The association of BKM120 and cetuximab with RT inhibited RT-induced activation of the MAPK pathway. CONCLUSION: These results can serve as a preclinical rationale for innovative treatments combining PI3K inhibition with anti-EGFR therapies and irradiation in patients with HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 151-159, 2017.

In vivo measurements with MOSFET detectors in oropharynx and nasopharynx intensity-modulated radiation therapy.

PURPOSE: To evaluate the feasibility of in vivo measurements with metal oxide semiconductor field effect transistor (MOSFET) dosimeters for oropharynx and nasopharynx intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: During a 1-year period, in vivo measurements of the dose delivered to one or two points of the oral cavity by IMRT were obtained with MOSFET dosimeters. Measurements were obtained during each session of 48 treatment plans for 21 patients, all of whom were fitted with a custom-made mouth plate. Calculated and measured values were compared. RESULTS: A total of 344 and 452 measurements were performed for the right and left sides, respectively, of the oral cavity. Seventy percent of the discrepancies between calculated and measured values were within +/-5%. Uncertainties were due to interfraction patient positions, intrafraction patient movements, and interfraction MOSFET positions. Nevertheless, the discrepancies between the measured and calculated means were within +/-5% for 92% and 95% of the right and left sides, respectively. Comparison of these discrepancies and the discrepancies between calculated values and measurements made on a phantom revealed that all differences were within +/-5%. CONCLUSION: Our experience demonstrates the feasibility of in vivo measurements with MOSFET dosimeters for oropharynx and nasopharynx IMRT.

Knock-down of hypoxia-induced carbonic anhydrases IX and XII radiosensitizes tumor cells by increasing intracellular acidosis.

The relationship between acidosis within the tumor microenvironment and radioresistance of hypoxic tumor cells remains unclear. Previously we reported that hypoxia-induced carbonic anhydrases (CA) IX and CAXII constitute a robust intracellular pH (pH(i))-regulating system that confers a survival advantage on hypoxic human colon carcinoma LS174Tr cells in acidic microenvironments. Here we investigate the role of acidosis, CAIX and CAXII knock-down in combination with ionizing radiation. Fibroblasts cells (-/+ CAIX) and LS174Tr cells (inducible knock-down for ca9/ca12) were analyzed for cell cycle phase distribution and survival after irradiation in extracellular pH(o) manipulations and hypoxia (1% O(2)) exposure. Radiotherapy was used to target ca9/ca12-silenced LS174Tr tumors grown in nude mice. We found that diminishing the pH(i)-regulating capacity of fibroblasts through inhibition of Na(+)/H(+) exchanger 1 sensitize cells to radiation-induced cell death. Secondly, the pH(i)-regulating function of CAIX plays a key protective role in irradiated fibroblasts in an acidic environment as accompanied by a reduced number of cells in the radiosensitive phases of the cell cycle. Thirdly, we demonstrate that irradiation of LS174Tr spheroids, silenced for either ca9 or both ca9/ca12, showed a respective 50 and 75% increase in cell death as a result of a decrease in cell number in the radioresistant S phase and a disruption of CA-mediated pH(i) regulation. Finally, LS174Tr tumor progression was strongly decreased when ca9/ca12 silencing was combined with irradiation in vivo. These findings highlight the combinatory use of radiotherapy with targeting of the pH(i)-regulating CAs as an anti-cancer strategy.

Dentalmaps: automatic dental delineation for radiotherapy planning in head-and-neck cancer.

PURPOSE: To propose an automatic atlas-based segmentation framework of the dental structures, called Dentalmaps, and to assess its accuracy and relevance to guide dental care in the context of intensity-modulated radiotherapy. METHODS AND MATERIALS: A multi-atlas-based segmentation, less sensitive to artifacts than previously published head-and-neck segmentation methods, was used. The manual segmentations of a 21-patient database were first deformed onto the query using nonlinear registrations with the training images and then fused to estimate the consensus segmentation of the query. RESULTS: The framework was evaluated with a leave-one-out protocol. The maximum doses estimated using manual contours were considered as ground truth and compared with the maximum doses estimated using automatic contours. The dose estimation error was within 2-Gy accuracy in 75% of cases (with a median of 0.9 Gy), whereas it was within 2-Gy accuracy in 30% of cases only with the visual estimation method without any contour, which is the routine practice procedure. CONCLUSIONS: Dose estimates using this framework were more accurate than visual estimates without dental contour. Dentalmaps represents a useful documentation and communication tool between radiation oncologists and dentists in routine practice. Prospective multicenter assessment is underway on patients extrinsic to the database.

Renaissance of contact x-ray therapy for treating rectal cancer.

Contact x-ray therapy (CXRT) with 50 kV has proven to be an efficient radiation therapy technique to achieve local control and rectal preservation for early rectal adenocarcinoma. Despite these results, CXRT has not been used due to the shortage of the no longer manufactured Philips RT 50™ unit. Recently, a new CXRT machine (Papillon 50™) became available on the market. This machine delivers a beam of 50 kV with a dose rate close to 15 Gy/min and has a percentage depth dose of 50% at 6-7 mm. The applicator size varies from 2-3 cm in diameter. Due to the original design of the main tube, treatment delivery is quick and more comfortable for the patients. An online viewing system incorporated in the tube allows a good visualization of the tumor with improved accuracy of radiation delivery. An international collaborative trial (Contact Endoscopic Microsurgery [CONTEM]) was set up to accrue approximately 300 cases of rectal adenocarcinoma staged T1, T2 or early T3 tumors in the UK, France, Denmark and Sweden. This trial should confirm the role of CXRT in curative treatment with organ preservation for early rectal cancers.

CyberKnife stereotactic radiotherapy for spinal tumors: value of computed tomographic myelography in spinal cord delineation.

OBJECTIVE: For para- and intraspinal tumors, precise spinal cord delineation is critical for CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiotherapy. We evaluated whether computed tomographic (CT) myelography is superior to magnetic resonance imaging (MRI) for accurate spinal cord delineation. Treatment parameters and short-term outcome and toxicity are also presented. METHODS: The planning CT scan, the gadolinium-enhanced, T1-weighted, 3-dimensional (3D) fast imaging employing steady-state acquisition MRI scan, and the CT myelogram were fused before volume-of-interest delineation. The planning target volume margin was less than 1 mm using the Xsight Spine tracking system (Accuray). We present data from 11 heavily pretreated patients who underwent CyberKnife stereotactic radiosurgery between November 2006 and January 2008. RESULTS: Spatial resolution was 0.46 and 0.93 mm/pixel for CT myelography and 3D-fast imaging employing steady-state acquisition MRI, respectively. The contrast between cerebrospinal fluid and spinal cord was excellent with CT myelography. A transient postmyelography headache occurred in 1 patient. The mean gross tumor volume was 51.1 mL. The mean prescribed dose was 34 Gy in 4 fractions (range, 2-7 fractions) with 147 beams (range, 79-232 beams) to the 75% reference isodose line (range, 68-80%), covering 95% (range, 86-99%) of the gross tumor volume with a mean conformity index of 1.4 (range, 1.1-1.8). No short-term toxicity on the spinal cord was noted at 1- to 6-months of follow-up. CONCLUSION: CT myelography was more accurate for spinal cord delineation than 3D-fast imaging employing steady-state acquisition MRI (used for its myelographic effect), particularly in the presence of ferromagnetic artifacts in heavily pretreated patients or in patients with severe spinal compression. Because other MRI sequences (T2 and gadolinium-enhanced T1) provide excellent tumor characterization, we suggest trimodality imaging for spinal tumor treatment to yield submillimetric delineation accuracy. Combined with CyberKnife technology, CT myelography can improve the feasibility of dose escalation or reirradiation of spinal tumors in selected patients, thereby increasing local control while avoiding myelopathy. Further follow-up and prospective studies are warranted.

Laparoscopic seminal vesicle and pelvic lymph node resection before high-dose three-dimensional conformal radiation therapy for localized prostate cancer. Results of a dosimetric study.

PURPOSE: To analyze the dosimetric implications of seminal vesicle (SV) resection at the time of laparoscopic pelvic lymph node (PLN) dissection in patients presenting with high-risk prostate cancer regarding PLN and SV involvement. PATIENTS AND METHODS: Between June and September 2005, twelve patients underwent laparoscopic SV resection and PLN dissection before delivering a total dose of 80 Gy through a three-dimensional conformal radiation therapy (3D-CRT). Dose-volume histograms (DVHs; rectum, bladder, femoral heads) were obtained from G1 (group 1 with SV) and G2 (group 2 without SV) according to either three- dimensional or intensity-modulated treatment planning. All DVH medians were compared using the nonparametric sign test. RESULTS: SV resection during laparoscopic PLN dissection was performed in all twelve patients without major complications. DVH obtained with three-dimensional and intensity-modulated treatment planning showed that the median doses of RV(25%) (25% of rectal volume), RV(50%), RFHV(5%) (5% of right femoral head volume) and LFHV(5%) (5% of left femoral head volume) in G1 were significantly higher compared to those obtained in G2. CONCLUSION: For patients presenting with high-risk prostate cancer, SV resection performed at the time of laparoscopic PLN dissection allows to significantly decrease the dose delivered to the rectum, using either three-dimensional or intensity-modulated treatment planning, and to reduce the risk of acute and late rectal toxicity.

[The cost of intensity modulated radiation therapy in head and neck cancers: results of the 2002 STIC study]. / Le coût de la radiothérapie conformationnelle avec modulation d'intensité dans les cancers ORL: l'étude STIC 2002.

An economic evaluation of intensity modulated radiotherapy (IMRT) in head and neck cancer was carried out to assess the cost of treatment and compare it to reimbursement paid to hospitals in the French Prospective Payment System. Planning required in average 20 hours of work for the physician and 6 hours for the radiation oncologist. Radiation consisted of 33 fractions in average and required 29 hours of work for the radiotherapy technician, 8 hours for the physician and 3 hours for the radiation oncologist. Mean cost of IMRT treatment was estimated at euro 10,916 (euro 2,773 for planning and euro 8,143 for radiation). The variability of costs was important and was in a large extent attributable to learning effects. As more patients were treated, unit cost of treatment was decreasing. In the French Prospective Payment System, mean reimbursement of IMRT was euro 6,987. For 70 % of the patients, reimbursement did not offset the cost of treatment. A financial support for hospitals implementing the technique is essential during the whole learning period.

Oxaliplatin-5-fluorouracil and ionizing radiation. Importance of the sequence and influence of p53 status.

OBJECTIVES AND METHODS: The association oxaliplatin (OXA)-5-fluorouracil/folinic acid (FUFA) is currently a standard first-line treatment for advanced colorectal cancer. The main objective of this experimental study was to examine the cytotoxic effects resulting from the addition of ionizing radiation (Rgamma) to the combination OXA-FUFA on 2 human colon cancer cell lines (SW403, p53 wild type and WiDr, p53 mutated). A clinically relevant drug sequence was used consisting in OXA during 2 h followed by FUFA over 24 h. The impact of the position of radiation (1 and 4 Gy) was tested: radiation 2 h before drug application, in the middle of the drug application or 24 h after the drug application. RESULTS: Both cell lines exhibited similar dose response curves to Rgamma alone, WiDr being more radio-sensitive than SW403 (IC50: 4.8 Gy and 7 Gy, respectively). The effects of Rgamma-drug combinations were assessed using a conventional isobolographic method and by computing a potentiation factor (F) defined as the ratio of IC50 drug combinations/IC50 drug combinations combined with Rgamma. The results from both calculation methods concurred: the combination of OXA-FUFA with Rgamma led to additive-antagonistic effects for the p53 mutated cell line (WiDr), whatever the sequence. In contrast, for the p53 wild type cell line (SW403), additive-synergistic effects were observed with, in this case, an optimal position for Rgamma occurring when applied before or at mid-drug application. CONCLUSIONS: These results could be taken into consideration for an optimal design of clinical protocols associating Rgamma and OXA-FUFA.