Reconstructive flap surgery in head and neck cancer patients: an interdisciplinary view of the challenges encountered by radiation oncologists in postoperative radiotherapy.

Background: Major advances have been made in reconstructive surgery in the last decades to reduce morbidity in head and neck cancer. Flaps are now present in 80% of patients with oral cavity cancer to cover anatomic, functional, and cosmetic needs. However, gaps in interdisciplinary innovation transfer from surgery to postoperative radiotherapy (poRT) remain challenging. We aimed to provide an interdisciplinary view of the challenges encountered by radiation oncologists in planning head and neck postoperative radiotherapy. Methods: A systematic and critical review was conducted to address areas of optimization in surgery and radiology that may be relevant to poRT. Results: Despite extensive surgical literature on flap techniques and salvage surgery, 13 retrospective series were identified, where flap outcomes were indirectly compared between surgery alone or poRT. These low-evidence studies suggest that radiotherapy accelerates flap atrophy, fibrosis, and osteoradionecrosis and deteriorates functional outcomes. Preliminary evidence suggests that tumor spread occurs at the flap-tissue junction rather than in the flaps. One prospective 15-patient study showed 31.3% vs. 39.2% flap volume reduction without or with poRT. In an international consensus, experts recognized the needs for optimized flap-sparing poRT against flap-related functional deterioration and bone damage. CT, MRI, and PET-CT modalities show potential for the delineation of the junction area between native tissues and flap for flap segmentation and to characterize flap-specific changes quantitatively and correlate them with patterns of relapse or complications. Conclusion: Flap management in poRT is insufficiently documented, but poRT seems to damage flaps. Current gaps in knowledge underscore the need for prospective flap assessment and interdisciplinary trials investigating flap morbidity minimization by flap-sparing poRT planning.

[Issues and implementation of postoperative radiotherapy after flap reconstructive surgery in head and neck cancers]. / Enjeux et mise en œuvre de radiothérapie postopératoire après chirurgie reconstructrice avec lambeau dans les cancers de la tête et du cou.

The management of head and neck cancers is multidisciplinary, often relying on the use of combined treatments to maximize the chances of cure. Combined treatments are however also responsible for cumulative side effects. The aim of reconstructive surgery with a flap is to restore a function lost with the loss of substance from the tumor resection. However, changes in reconstructive surgery have impact of postoperative radiotherapy planning. The optimization of imaging protocols for radiotherapy planning should make it possible to identify postoperative changes and to distinguish flaps from surrounding native tissues to delineate the flaps and document the spontaneous evolution of these flaps or dose-effect relationships in case of radiotherapy. Such changes include atrophy, fibrosis of soft tissue flaps and osteoradionecrosis of bone flaps. Radiotherapy optimization also involves standardization of the definition of target volumes in situations where a flap is present, a situation that is increasingly common in routine care. This evolution of practice, beyond the essential multidisciplinary consultation meetings defining treatment indications, requires a close radio surgical collaboration with respect to technical aspects of the two disciplines. Doing so, anticipation of relapse and toxicity profiles could possibly lead to propose strategies for personalized de-escalation of multimodal treatments through interdisciplinary trials.

Need for standardization in the use of structures in the intensity-modulated radiation therapy planning of head and neck cancers, a GORTEC study.

BACKGROUND: Most radiotherapy structures contoured on CT scans during IMRT planning are defined by the ICRU, forming part of standard practice. Associated dose-volume constraints serve as parameters for dose computation algorithms to produce optimized dose maps. On the ground, however, physicists/dosimetrists routinely delineate auxiliary "non-standard" radiotherapy structures (nsRS). MATERIALS/METHODS: From 287 patients' data, five categories of nsRS were identified. Inter-center, inter-patient variability, and temporal trends in nsRS use were investigated. Relation of nsRS with topological complexity, plan quality, calculated quality assurance (QA) and expert QA, was investigated using machine learning classification. RESULTS: nsRS accounted for 19.2% of all structures. Average number of nsRS per patient was 8.92 ± 6.70. Variation coefficient across centers was > 70% for nsRS frequency. There was no effect of patient volume per center on averaged nsRS number between low, intermediate, and high-volume centers. No temporal trends in nsRS use were detected at the high-volume centers, except for an increase in 'forced-dose' nsRS (p = 3.08 × (10)^(-5)) at one center. Machine learning prediction accuracy including nsRS features were 0.70 ± 0.06 for topological complexity, 0.58 ± 0.05 for calculated QA and 0.72 ± 0.05 for expert QA. CONCLUSION: Use of nsRS is frequent but heterogeneous and should be standardized further in line with ICRU initiatives in IMRT planning. Use of nsRS should be documented with respect to the need for nsRS from dose computation algorithms of treatment planning systems and IMRT machines in terms of modulation capacity and plan robustness.

Feasibility and early toxicity of intraoperative radiotherapy for breast cancer using the papillon + system: First results.

Background and Purpose: Breast intra operative radiation therapy has been evaluated with different systems delivering 20-21 Gy with treatment times around 30 min. Papillon + TM Contact X-ray machine was designed to produce a 50 kVp beam with a high dose rate ≥ 15 Gy/minute. A pilot study with the first prototype was conducted in Nice. Materials and methods: The inclusion criteria were age ≥ 60 years, unifocal ductal breast adenocarcinoma ≤ 2.5 cm, grade 1-2. Surgical local excision with sentinel node dissection was performed and the applicator was placed in the tumor bed after excision with a prescribed dose of 20 Gy. The main end point of the study was the doses measured with the Gafchromic films; two were located at the skin surface and two in the excision cavity. Secondary endpoints were early toxicity and relapse free survival. Results: Between 10/2018 and 09/2019, 26 patients were included. Mean Gafchromic doses were 18.8 Gy ± 2 Gy at the south pole, 15.6 Gy ± 2.81 Gy at the equator and 2.5 Gy ± 1.67 Gy at the skin. With a median follow-up time of 12 months, no skin or subcutaneous toxicity > grade 2, no local relapse and no metastasis were observed. Conclusion: This is the first phase II study testing the Papillon + tm system for breast IORT with in vivo dosimetry measurements and reassuring clinical data.

Targeted Radiotherapy Using Contact X-ray Brachytherapy 50 kV.

Rectal adenocarcinoma is a quite radioresistant tumor. In order to achieve non-operative management (NOM) radiotherapy plays a major role. Targeted radiotherapy aiming at high precision 3D radiotherapy uses stereotactic image-guided external beam radiotherapy machines. To further safely increase the tumor dose, endocavitary brachytherapy (ECB) is an original approach. There are two different ways to perform such an ECB: contact X-ray brachytherapy (CXB) using a 50 kV X-ray generator with an X-ray tube positioned under eye guidance into the rectal cavity and high-dose-rate brachytherapy (HDRB) using iridium-192 sources positioned into the rectal cavity under image guidance. This study focused on CXB. CXB uses a small mobile generator that produces 50 kV X-rays with limited penetration. This technique is well adapted to accessible tumors of limited size and especially needs a high dose rate (≥15 Gy/minutes) for rectal tumors. It is performed on an ambulatory basis. A total dose between 80−110 Gy is delivered in 3−4 fractions over 3 to 6 weeks into a small volume (5 cm3). CXB was pioneered in the 1970s by Papillon using the Philips RT 50TM. Since 2009, the Papillon P50TM has been used in 11 institutions in Europe. The OPERA Phase III trial tested the hypothesis that a CXB boost (90 Gy/3 fr) compared to an EBRT boost (9 Gy/5 fr) for T2−T3 ab < 5 cm and N0−N1 < 8 mm will increase the 3-year organ preservation (OP) rate when combined with 45 Gy/5 weeks with concomitant capecitabine. Out of more than 300 patients with tumors < 3 cm (1962−1992), Papillon reported a long-term local control close to 85%. Similar results were published in Europe and USA at that time. The Lyon R96-2 Phase III trial (2004) demonstrated that, when combined with preoperative EBRT, a CXB boost (90 Gy/3 fr) significantly increased the rate of clinical complete response (cCR) and sphincter preservation, with some patients having OP at 10 years. With more than 2000 patients treated in Europe (2010−2020) using the Papillon 50TM, organ preservation appears possible in close to 80% of cases in selected early T2−T3. The OPERA trial closed after 141 inclusions (2015−2020) after an independent data monitoring committee recommendation because of promising results. At the 2-year follow-up (blinded data), the rate of cCR and OP were 77% and 72%, respectively, for the 141 tumors, and for T < 3 cm (61 pts), they were 86% and 85%, respectively, with good bowel function. The final results should be available in 2022. Organ preservation using NOM appears to be a promising approach for rectal cancer. A CXB boost with chemoradiotherapy in selected early T2−T3 could become an attractive option to achieve a planned OP. This approach should be proposed to well-informed patients after discussion in an MDT.

Propensity score analysis of radical proctectomy versus organ preservation using contact X-ray brachytherapy for rectal cancer.

INTRODUCTION: Radical proctectomy (RP-TME) with neo adjuvant chemoradiotherapy (nCRT) remains the standard treatment for T2-T3 rectal cancer. Organ preservation (OP) using CRT and a "watch and wait" strategy (W&W) is a field of research. Planned organ preservation can be proposed for early T1-T3 using contact X-ray brachytherapy (CXB). We compared the oncological outcomes of both approaches using a propensity score matched-cohort analysis. MATERIAL AND METHODS: For comparative analyses between patients with nCRT + RP-TME and patients with CXB + CRT, propensity scores were calculated with logistic regression and multiple imputations for missing data. The variables included in the propensity score model were PS status, T-N stage and rectal circumference extension. Patients were matched 1:1 using the nearest neighbor method with a 0.1 caliper restriction. The 5-year Cancer Specific survival was the primary end point. RESULTS: The Accord 12 phase III trial included 584 patients who treated with nCRT + RP-TME. The CXB cohort included 71 patients with a planned OP. To select OP patient candidate, T4, tumor with extension >66% circumference were eliminated and only patients treated with CXB + CRT were analyzed in the CXB cohort resulting in a total of 374 patients. A one to one paired cohort with 36 patients in each group was derived. These two cohorts were well matched for all confounding factors except for age. The 5-year cancer specific rate showed no significant difference between the two groups (89% in Accord 12 vs 82% in CXB; p = 0.84). At 5 years, rate of metastasis (15% vs 22%, p = 0.54) showed no significant difference. In the CXB group 33/36 patients preserved their rectum. CONCLUSION: The organ preservation strategy using CXB boost yielded a 5-year cancer specific survival rate similar to patients treated with RP-TME. In selected early T2-3 rectal adenocarcinoma an organ preservation strategy could be offered as a reasonable option.

Postsurgical geometrical variations of tumor bed and brainstem during photon and proton therapy for pediatric tumors of the posterior fossa: dosimetric impact and predictive factors.

PURPOSE: Brainstem radionecrosis is an important issue during the irradiation of tumors of the posterior fossa. The aim of the present study is to analyze postsurgical geometrical variations of tumor bed (TB) and brainstem (BS) and their impact on dosimetry. METHODS: Retrospective collection of data from pediatric patients treated at a single institution. Availability of presurgical magnetic resonance imaging (MRI) was verified; availability of at least two postsurgical MRIs was considered a further inclusion criterion. The following metrics were analyzed: total volume, Dice similarity coefficient (DSC), and Haudsdorff distances (HD). RESULTS: Fourteen patients were available for the quantification of major postsurgical geometrical variations of TB. DSC, HD max, and HD average values were 0.47 (range: 0.08;0.76), 11.3 mm (7.7;24.5), and 2.6 mm (0.7;6.7) between the first and the second postoperative MRI, respectively. Postsurgical geometrical variations of the BS were also observed. Coverage to the TB was reduced in one patient (D95: -2.9 Gy), while D2 to the BS was increased for the majority of patients. Overall, predictive factors for significant geometrical changes were presurgical gross tumor volume (GTV) > 33 mL, hydrocephaly at diagnosis, Luschka foramen involvement, and younger age (≤ 8 years). CONCLUSION: Major volume changes were observed in this cohort, with some dosimetric impact. The use of a recent co-registration MRI is advised. The 2-3 mm HD average observed should be considered in the planning target volume/planning organ at risk volume (PTV/PRV) margin and/or robust optimization planning. Results from wider efforts are needed to verify our findings.

Comparison of 3 γ-probes for simultaneous iodine-125-seed and technetium-99m breast cancer surgery: NEMA standard characterisation with extended processing.

PURPOSE: Iodine-125 (125I) seeds can be used as landmarks to locate non-palpable breast lesions instead of implanting metal wires. This relatively new technique requires a nuclear probe usually used for technetium-99m (99mTc) sentinel node detection. This study aimed to compare the performances of different probes and valid the feasibility of this technique, especially in the case of simultaneous 125I-seed and 99mTc breast cancer surgery. METHODS: Three probes with different features (SOE-3211, SOE-3214 and GammaSUP-II) were characterised according to the NEMA NU3-2004 standards for a 99mTc source and a 125I-seed. Several tests such as sensitivity, linearity or spatial resolution allowed an objective comparison of their performances. NEMA testing was extended to work on signals discrimination in case of simultaneous detection of two different sources (innovative figure of merit "Shift Index") and to assess the 99mTc scatter fraction, a useful parameter for the improvement of the probes in terms of detector materials and electronic system. RESULTS: Although the GammaSUP-II probe saturated at a lower activity (1.6 MBq at 10 mm depth), it allowed better sensitivity and spatial resolution at the different NEMA tests performed with the 99mTc source (7865 cps/MBq and 15 mm FWHM at 10 mm depth). With the 125I-seed, the GammaSUP-II was the most sensitive probe (3106 cps/MBq at 10 mm depth) and the SOE-3211 probe had the best spatial resolution (FWHM 20 mm at 10 mm depth). The SOE-3214 probe was more efficient on discriminating 125I from 99mTc in case of simultaneous detection. The SOE probes were more efficient concerning 99mTc scatter fraction assessments. The SOE-3211 probe, with overall polyvalent performances, seemed to be an interesting trade-off for detection of both 125I and 99mTc. CONCLUSION: The three probes showed heterogeneous performances but were all suitable for simultaneous 99mTc sentinel node and 125I-seed detection. This study provides an objective and innovative methodology to compare probes performances and then choose the best trade-off regarding their expected use.

Targeting Gap Junctions: New Insights into the Treatment of Major Depressive Disorder.

BACKGROUND: Major depressive disorder (MDD) is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and associated with excess mortality. Treatments for this disease are not effective in all patients showing the need to find new therapeutic targets. OBJECTIVE: This review aims to update our knowledge on the involvement of astroglial gap junctions and hemichannels in MDD and to show how they have become potential targets for the treatment of this pathology. METHODS: The method applied in this review includes a systematic compilation of the relevant literature. RESULTS AND CONCLUSION: The use of rodent models of depression, gene analysis of hippocampal tissues of MDD patients and post-mortem studies on the brains from MDD patients suggest that astrocytic gap junction dysfunction may be a part of MDD etiologies. Chronic antidepressant treatments of rats, rat cultured cortical astrocytes and human astrocytoma cell lines support the hypothesis that the up-regulation of gap junctional coupling between astrocytes could be an underlying mechanism for the therapeutic effect of antidepressants. However, two recent functional studies suggest that connexin43 hemichannel activity is a part of several antidepressants' mode of action and that astrocyte gap junctional intercellular communication and hemichannels exert different effects on antidepressant drug response. Even if they emerge as new therapeutic targets for new and more active treatments, further studies are needed to decipher the sophisticated and respective role of astrocytic gap junctions and hemichannels in MDD.

Planned organ preservation for early T2-3 rectal adenocarcinoma: A French, multicentre study.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) and watch-and-wait policy as reported by Habr-Gama are references for organ preservation in rectal cancer. To increase the clinical complete response (cCR) and reduce the local recurrence rates, we report a retrospective analysis of a prospective cohort of selected T2-3 tumours treated in three French institutions using contact X-ray brachytherapy (CXB) with nCRT. METHODS: Tumour selection was based on digital rectal examination (DRE), rigid rectoscopy, magnetic resonance imaging (MRI) and/or endorectal ultrasound. Adenocarcinoma T2-3 < 5 cm largest diameter, M0 were treated, all with organ preservation intent. CXB delivering 90 Gy/3 fractions/4 weeks was combined with CRT (capecitabine 50). Strict evaluation of tumour response using DRE and rectoscopy ± MRI was performed at regular interval with prolonged surveillance. FINDINGS: Between 2002 and 2016, 74 consecutive patients were treated (median age: 74 years. T2: 45 and T3: 29). A cCR or near-cCR (mainly rectal wall ulceration) was noted at week 14 in 71 patients (95%). A local excision was performed in 13 patients. Of three partial responses (PRs), one salvage anterior resection was performed. With a median follow-up of 3 years, local recurrence (mainly in the rectal wall) was seen in seven patients. The 3-year local recurrence rate was 10%, and the cancer-specific survival, 88%. Two patients underwent radical proctectomy for PR or local recurrence and 96% preserved their rectum. Grade III acute toxicity was recorded in five patients. Rectal bleeding was the main late toxicity (grade III in 12%). Bowel function was scored as good or excellent in 85% of patients. INTERPRETATION: Combining CXB and nCRT in selected early T2-T3 rectal cancers may safely provide a high rate of cCR, organ preservation, and good bowel function with a risk of local recurrence below 15%. Such an approach could be offered to operable patients as a planned option for organ preservation.

Connexin43- and Pannexin-Based Channels in Neuroinflammation and Cerebral Neuropathies.

Connexins (Cx) are largely represented in the central nervous system (CNS) with 11 Cx isoforms forming intercellular channels. Moreover, in the CNS, Cx43 can form hemichannels (HCs) at non-junctional membrane as does the related channel-forming Pannexin1 (Panx1) and Panx2. Opening of Panx1 channels and Cx43 HCs appears to be involved in inflammation and has been documented in various CNS pathologies. Over recent years, evidence has accumulated supporting a link between inflammation and cerebral neuropathies (migraine, Alzheimer's disease (AD), Parkinson's disease (PD), major depressive disorder, autism spectrum disorder (ASD), epilepsy, schizophrenia, bipolar disorder). Involvement of Panx channels and Cx43 HCs has been also proposed in pathophysiology of neurological diseases and psychiatric disorders. Other studies showed that following inflammatory injury of the CNS, Panx1 activators are released and prolonged opening of Panx1 channels triggers neuronal death. In neuropsychiatric diseases, comorbidities are frequently present and can aggravate the symptoms and make therapeutic management more complex. The high comorbidity between some neuropathies can be partially understood by the fact that these diseases share a common etiology involving inflammatory pathways and Panx1 channels or Cx43 HCs. Thus, anti-inflammatory therapy opens perspectives of targets for new treatments and could have real potential in controlling a cerebral neuropathy and some of its comorbidities. The purpose of this mini review is to provide information of our knowledge on the link between Cx43- and Panx-based channels, inflammation and cerebral neuropathies.

Radiotherapy staffing in the European countries: final results from the ESTRO-HERO survey.

BACKGROUND: The ESTRO Health Economics in Radiation Oncology (HERO) project has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The first milestone was to assess the availability of radiotherapy resources within Europe. This paper presents the personnel data collected in the ESTRO HERO database. MATERIALS AND METHODS: An 84-item questionnaire was sent out to European countries, through their national scientific and professional radiotherapy societies. The current report includes a detailed analysis of radiotherapy staffing (questionnaire items 47-60), analysed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis was conducted between February and July 2014, and is based on validated responses from 24 of the 40 European countries defined by the European Cancer Observatory (ECO). RESULTS: A large variation between countries was found for most parameters studied. Averages and ranges for personnel numbers per million inhabitants are 12.8 (2.5-30.9) for radiation oncologists, 7.6 (0-19.7) for medical physicists, 3.5 (0-12.6) for dosimetrists, 26.6 (1.9-78) for RTTs and 14.8 (0.4-61.0) for radiotherapy nurses. The combined average for physicists and dosimetrists is 9.8 per million inhabitants and 36.9 for RTT and nurses. Radiation oncologists on average treat 208.9 courses per year (range: 99.9-348.8), physicists and dosimetrists conjointly treat 303.3 courses (range: 85-757.7) and RTT and nurses 76.8 (range: 25.7-156.8). In countries with higher GNI per capita, all personnel categories treat fewer courses per annum than in less affluent countries. This relationship is most evident for RTTs and nurses. Different clusters of countries can be distinguished on the basis of available personnel resources and socio-economic status. CONCLUSIONS: The average personnel figures in Europe are now consistent with, or even more favourable than the QUARTS recommendations, probably reflecting a combination of better availability as such, in parallel with the current use of more complex treatments than a decade ago. A considerable variation in available personnel and delivered courses per year however persists among the highest and lowest staffing levels. This not only reflects the variation in cancer incidence and socio-economic determinants, but also the stage in technology adoption along with treatment complexity and the different professional roles and responsibilities within each country. Our data underpin the need for accurate prediction models and long-term education and training programmes.

Involvement of gap junction channels in the pathophysiology of migraine with aura.

Migraine is a common, recurrent, and disabling primary headache disorder with a genetic component which affects up to 20% of the population. One third of all patients with migraine experiences aura, a focal neurological disturbance that manifests itself as visual, sensitive or motor symptoms preceding the headache. In the pathophysiology of migraine with aura, activation of the trigeminovascular system from the meningeal vessels mediates migraine pain via the brainstem and projections ascend to the thalamus and cortex. Cortical spreading depression (CSD) was proposed to trigger migraine aura and to activate perivascular trigeminal nerves in the cortex. Quinine, quinidine and the derivative mefloquine are able to inhibit CSD suggesting an involvement of neuronal connexin36 channels in CSD propagation. More recently, CSD was shown to induce headache by activating the trigeminovascular system through the opening of stressed neuronal Pannexin1 channels. A novel benzopyran compound, tonabersat, was selected for clinical trial on the basis of its inhibitory activity on CSD and neurogenic inflammation in animal models of migraine. Interestingly, in the time course of animal model trials, tonabersat was shown to inhibit trigeminal ganglion (TGG) neuronal-glial cell gap junctions, suggesting that this compound could prevent peripheral sensitization within the ganglion. Three clinical trials aimed at investigating the effectiveness of tonabersat as a preventive drug were negative, and conflicting results were obtained in other trials concerning its ability to relieve attacks. In contrast, in another clinical trial, tonabersat showed a preventive effect on attacks of migraine with aura but had no efficacy on non-aura attacks. Gap junction channels seem to be involved in several ways in the pathophysiology of migraine with aura and emerge as a new promising putative target in treatment of this disorder.

[Advances in radiation oncology for metastatic bone disease]. / Métastases osseuses : les nouvelles techniques d'irradiation et traitements combinés ablatifs décalent-ils les standards ?

INTRODUCTION: Irradiation of bone metastases primarily aims at alleviating pain, preventing fracture in the short term. The higher doses and more conformal dose distribution achievable while saving healthy tissue with new irradiation techniques have induced a paradigm shift in the management of bone metastases in a growing number of clinical situations. MATERIALS AND METHODS: A search of the English and French literature was conducted using the keywords: bone metastases, radiotherapy, interventional radiology, vertebroplasty, radiofrequency, chemoembolization. RESULTS-DISCUSSION: Stereotactic irradiation yields pain relief rates greater than 90% in Phase I/II and retrospective studies. IMRT (static, rotational, helical) and stereotactic irradiation yield local control rates of 75-90% at 2 years. Some situations previously evaluated as palliative are currently treated more aggressively with optimized radiation sometimes combined modality interventional radiology. CONCLUSION: A recommendation can only be made for stereotactic irradiation in vertebral oligometastases or reirradiation. In the absence of a sufficient level of evidence, the increasing use of conformal irradiation techniques can only reflect the daily practice and the patient benefit while integrating economic logic care. The impact of these aggressive approaches on survival remains to be formally demonstrated by interventional prospective studies or observatories including quality of life items and minimal 2-year follow-up.

Interstitial preoperative high-dose-rate brachytherapy for early stage cervical cancer: dose-volume histogram parameters, pathologic response and early clinical outcome.

PURPOSE: To analyze dose-volume histogram parameters and pathologic response after preoperative high-dose-rate brachytherapy (HDRB) for high-risk early stage cervical cancers (ESCCs). METHODS AND MATERIALS: From June 2007 to December 2011, 32 patients with a histologically proven invasive cervical cancer with high risk of local recurrence (size >2cm, adenocarcinoma type, perineural and/or lymphovascular invasion) underwent a preoperative HDRB, which delivered a total dose of 39Gy in nine fractions over 5 days. All the patients underwent hysterectomy after HDRB. RESULTS: With a median clinical target volume of 50cc (minimum-maximum, 42-74), the median V100 was 49cc (minimum-maximum, 42-50). Median D90 was 45Gy (equivalent dose at 2Gy per fraction, 56Gyαß10). Median D2cc was 34Gy, 31Gy, 28Gy, and 38Gyαß3 for bladder, rectum, sigmoid, and vagina, respectively. Twenty-eight patients (88.5%) achieved a complete histologic response after surgery, whereas for the 4 remaining patients, residual tumor cells (3 patients) and gross residual disease (1 patient) were observed in the pathologic specimen. With a median followup of 24 months (minimum-maximum, 5-48), no local recurrence was observed; 1 patient died of intercurrent cause. Early toxicity occurred within the 30 days after HDRB (Common Terminology Criteria for Adverse Events v3.0) was G1 diarrhea for 15 patients (47%) and G1 urinary frequency or urgency for 13 patients (40.6%). No G2-G3 toxicities were noticed. CONCLUSIONS: Preoperative HDRB for high-risk ESCCs represents a well-tolerated procedure, which leads to a high rate of postoperative pathologic response. Dose-volume histogram parameters were at least equivalent to those obtained with a low-dose-rate procedure. Long-term results will help to analyze the place of preoperative brachytherapy in the management of high-risk ESCCs.

High-dose pre-operative helical tomotherapy (54 Gy) for retroperitoneal liposarcoma.

PURPOSE: To evaluate the feasibility of pre-operative radiotherapy (54 Gy) with Helical Tomotherapy (HT) followed by surgery. METHODS AND MATERIALS: Ten patients with non-metastatic resectable retroperitoneal liposarcomas were treated by pre-operative tomotherapy (54 Gy) and surgery. Clinical and biological toxicities were evaluated on the CTCAEV3.0 scale. For nine patients, delivered tomotherapy plans were compared with retrospectively-planned dynamic intensity-modulated radiotherapy (IMRT) dosimetric studies. RESULTS: No immediate or late Grade>2 toxicities were observed after radiotherapy. Post-operatively, one patient died and three patients experienced Grade 3 toxicity (two digestive and one metabolic). These toxicities disappeared and only two patients presented persistent Grade 1 paresthesia. R0 resection was obtained for four patients, R1 for four, and R2 resection for two. With a median follow-up of 26 months, no local or metastatic relapse was observed. Dosimetric comparisons between HT and retrospectively-planned IMRT demonstrate adequate target volume coverage for both techniques. Gastrointestinal sparing is higher with HT with a D200cc reduced by 5 Gy. Integral dose (ID) was increased in HT. CONCLUSIONS: High dose pre-operative radiotherapy (54 Gy) for retroperitoneal liposarcoma is feasible and mostly well tolerated. Cumulative toxicity and tolerance depend mainly on patient's general status. Image-guided radiation therapy (IGRT) is essential, irrespective of the IMRT technique used. Furthermore, HT offers the possibility of sparing selected areas in such complex volumes.

Dose gradient impact on equivalent dose at 2 Gy for high dose rate interstitial brachytherapy.

PURPOSE: To evaluate a new calculation model estimating the equivalent dose at 2 Gy (EQD2) taking into account dose gradient in high dose rate interstitial brachytherapy (HDRIB). MATERIAL AND METHODS: Forty dose-volume histograms (DVHs) of breast (20 pts) and prostate (20 pts) cancer dose distributions were reviewed. Physical prescribed doses (PPD) were 34 Gy (10f/5d) and 18 Gy (6f/2d) for breast (partial irradiation protocol) and prostate (boost after external irradiation) treatment, respectively. For each DVH, clinical target volume (CTV), V100, V150, V200, D90 and D100 were determined. Based on DVH segmentation, elementary doses (d) delivered to elementary volumes were determined, then multiplied by C (% of CTV receiving d). According to the linear quadratic model, EQD2 was calculated for different α/ß ratios. RESULTS: For breast implant, median EQD2 (α/ß = 4) was 42 Gy and 76 Gy (66-85) without and with dose gradient consideration, respectively. For prostate implant, median EQD2 (α/ß = 1.5) was 39 Gy and 98 Gy (90-103) whether dose gradient was not or was taken into account, respectively. CONCLUSIONS: This study pointed out that for brachytherapy, EQD2 calculation must take into account the dose gradient. Because this model is a mathematical one, it has to be cautiously applied. Nevertheless, it appears as a useful tool for EQD2 comparison between the same PPD delivered through EBRT or brachytherapy regarding trial result interpretation.

Two-year clinical experience with tomotherapy: the French national cancer institute project on implementing new technology.

The pooled 2-year clinical experience using three tomotherapy units installed in France in 2007 is presented. Treatment indications and protocols were devised for each disease site and were the result of a consensus. A total of 642 patients were treated for central nervous system, head and neck, thoracic, abdominal, and pelvic tumors. Overall, grade 3, 4, and 5 acute toxicity was 10.7%, 0.3%, and 0.2%, respectively. Grade 3 chronic toxicity was 1.2%. There was no grade 4 or 5 chronic toxicity. The use of tomotherapy in a broad clinical practice is safe, and acute and chronic toxicity both are acceptable for all anatomical locations.