Hyperfractionated Accelerated Radiotherapy Research Articles

Hyperfractionated Accelerated Radiotherapy Versus Stereotactic Body Radiotherapy in the Treatment of Limited-Stage Small Cell Lung Cancer: A Matched-Pair Analysis.

Concurrent chemoradiotherapy based on hyperfractionated accelerated radiotherapy (HART) is the first-line recommended regimen for the treatment of small-cell lung cancer (SCLC). However, Stereotactic Body Radiotherapy (SBRT) is also regarded as an effective treatment for limited-stage (LS) SCLC, and the efficacy and safety of HART versus SBRT stay controversial. In this study, 188 LS-SCLC patients were retrospectively divided into two groups receiving chemotherapy combined with either HART or SBRT. In HART group, patients received 4500 cGy in 30 fractions, administered twice daily for 3 weeks. Whereas in the SBRT group, a total radiation dose of 4000-4500 cGy was delivered in 10 fractions over 2 weeks. Thirty-three pairs of patients were finally included for next analysis. The estimated objective response rates were 63.6 % (21/33) and 78.8 % (26/33) in HART group and SBRT group, respectively (P = 0.269). Furthermore, there was no significant difference between HART and SBRT groups in overall survival (26 months vs. 29 months, P = 0.362) and progression free survival (11 months vs. 15 months, P = 0.223). As for the adverse events, toxicity of both groups is similar and slight that no grade 4 event was observed. Grade 3 pneumonitis cases were all occurred in the HART group (9.1%, 3/33, P = 0.238), and grade 3 esophagitis cases were all occurred in the SBRT group (6.1%, 2/33, P = 0.492). Compared with HART, SBRT could be another effective treatment with satisfactory safety for the concurrent chemoradiotherapy in patients with LS-SCLC.

Prise en charge des cancers bronchiques à petites cellules de stade localisé, actualisation: Management of limited-stage small cell lung cancer, an update

Limited-stage small cell lung cancer (LS-SCLC) represents 15-20% of all lung cancers, and because of its rapid tumor kinetics, less than a third of SCLC are discovered at limited stage. The different steps and modalities of its management are well defined and codified. They involve a comprehensive staging assessment using CT scans of the chest, abdomen, and pelvis, PET-CT scans, and ideally brain imaging using MRI to avoid missing a more extensive stage of the disease, which would significantly alter the treatment strategy. The treatment consists of a combination of chemotherapy with platinum/ etoposide and radiotherapy, possibly delivered in a hyperfractionated schedule with two daily sessions. SCLC is particularly both chemosensitive and radiosensitive, so that the initial evaluation shows frequently a complete response, and prophylactic cranial irradiation (PCI) is then recommended. Relapses are unfortunately frequent, less responsive to second line treatments, and therapeutic options are limited. No targeted agents or immunotherapy have robustly demonstrated efficacy in the treatment of LS-SCLC. Even if hyperfractionated accelerated radiotherapy (HFART) at the dose of 45Gy in 30 fractions has given the best results, most clinicians use once-daily chemoradiation regimen (60-70Gy). Studies have evaluated dose escalation either with HFRAT or with conventional fractionation (66 to 70Gy). Several trials are currently investigating the addition of immunotherapy to chemoradiation, hippocampus sparing PCI or the omission of PCI. In rare cases of very early stage SCLC, surgery or stereotactic radiotherapy may be envisaged.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Association of 3D-CRT and IMRT accelerated hyperfractionated radiotherapy with local control rate and 5-year survival in esophageal squamous cell carcinoma patients.

This retrospective study examined the relevance and prognostic factors of whole-course conformal radiotherapy (CRT) and late-course accelerated hyperfractionation radiotherapy (LCAFRT) for esophageal squamous cell carcinoma (ESCC). A total of 110 patients with ESCC received whole-course CRT and LCAFRT between May 2004 and January 2015. All patients received conventional CRT of 2 Gy per day, up to 30-40 Gy, followed by LCAFRT using reduced fields at 1.5 Gy/fraction twice a day, up to 24-39 Gy, for a total dose of 60-69 Gy. The median follow-up was 85 months. The whole groups 1-, 3-, and 5-year survival rates were 81.8%, 46.4%, and 41.8%, respectively. The local control rates for the whole group at 1, 3, and 5 years were 82.7%, 70.0%, and 68.2%, respectively. There were no significant differences among survival rates and local control rates between the 3D-CRT and intensity-modulated radiotherapy (IMRT) groups. The main reactions to acute radiotherapy were acute radiation tracheitis, esophagitis, and pneumonia. The tumor location and TNM stage were independent prognostic factors for overall survival. The results showed that whole-course CRT and LCAFRT for ESCC can improve survival and local control with a tolerable acute reaction compared to previous studies. Local recurrence and distant metastasis are the main failure modes of treatment. Whole-course CRT and LCAFRT for ESCC can improve the survival and local control rate compared with previous studies from the 2DRT era. It might provide another treatment for patients with inoperable ESCC or refusing surgery.

Evaluation of efficacy and tolerance of radical radiotherapy and radiochemotherapy in treatment of locally advanced, unresectable rectal cancer.

133 Background: Evaluation of tolerance and efficacy of two schemes of neoadjuvant treatment in patients with unresectable rectal cancer: radiochemotherapy and radiotherapy, including conventional and accelerated hyperfractionation. Methods: 145 patients (pts) with unresectable, locally advanced rectal cancer. Schemes used: radiotherapy (RT) in 73 (50%) or radiochemotherapy (CRT) in 72 (50%). In RT group conventional fractionation (CFRT) and hyperfractionated accelerated radiotherapy (HART). In CRT 54 Gy in 1.8 Gy fractions was given with two cycles of 5 Fu-LV chemotherapy in three or five day cycles. Results: Objective response (OR) in RT and CRT group was 60% versus 75%. Resection rate (RR) in RT and CRT: 37% versus 65%. Tumor mobility and laparotomy-based unresectability were significant factors for OR. Performance status, tumor mobility, neoadjuvant treatment method were significant for RR. Five-year LC in CRT versus RT: 68% versus 37%. Five-year OS: 52% versus 27%. CRT was independent positive prognostic factor for resection rate, local control. Tumor volume did not reach significance for any of the end points. Lenght of chemotherapy cycles (three or five days) did not reach significance for any of the endpoints. Toxicity was acceptable in both groups. CRT had best outcome in LC: 68% versus 42% in HART; and 25% in CFRT. Five-year OS was much better in CRT than in CFRT: 52% versus 17%. Conclusions: The results of treatment depend on performance status, patients age, tumor mobility and unresectability based on earlier laparotomy. The lack of influence of the tumor volume on all endpoints indicates the need for radical neoadjuvant treatment independently of tumor volume and underlines the key role of a proper surgical treatment. In patients not suitable for CRT, HART is optimal strategy for its better efficacy than CFRT.

Evaluation of Efficacy and Tolerance of Radical Radiotherapy and Radiochemotherapy in Treatment of Locally Advanced, Unresectable Rectal Cancer.

Background: A retrospective evaluation of tolerance and efficacy of two schemes of neoadjuvant treatment in patients (pts) with unresectable rectal cancer: radiochemotherapy (CRT) and radiotherapy (RT), including conventional and accelerated hyperfractionation. Material and Method: A total of 145 consecutive pts with unresectable, locally advanced rectal cancer. The schemes used are RT in 73 (50%) or CRT in 72 (50%). In CRT, 54 Gy in 1.8 Gy fractions was given with chemotherapy, In the RT group, conventional fractionation (CFRT) and hyperfractionated accelerated radiotherapy (HART). HART was introduced at first as an alternative to CFRT, after radiobiological studies suggesting a therapeutic gain of hyperfractionation in other cancers, and second to administer relatively high dose needed in unresectable cancer, which is not feasible in hypofractionation because of critical organs sensitivity to high fraction doses (fd). HART was an alternative option in pts with medical contraindications to chemotherapy and to shorten overall treatment time with greater radiobiological effectiveness than CFRT. Results: Objective response (OR) in the RT and CRT group was 60% versus 75%. Resection rate (RR) in RT and CRT: 37% versus 65%. Tumor mobility and laparotomy-based unresectability were significant factors for OR. Performance status (PS), tumor mobility, and neoadjuvant treatment method were significant for RR.

Dose escalation in advanced floor of the mouth cancer: a pilot study using a combination of IMRT and stereotactic boost

PurposeWe evaluated the efficiency and toxicity of stereotactic hypofractionated boost in combination with conventionally fractionated radiotherapy in the treatment of advanced floor of the mouth cancer.MethodsThirty-seven patients with advanced stage of the floor of the mouth cancer, histologically confirmed squamous cell carcinoma (p16 negative) ineligible for surgical treatment, were indicated for radiochemotherapy or hyperfractionated accelerated radiotherapy (HART). The radiotherapy protocol combined external beam radiotherapy (EBRT) and a stereotactic hypofractionated boost to the primary tumor. The dose delivered from EBRT was 70–72.5 Gy in 35/50 fractions. The hypofractionated boost followed with 10 Gy in two fractions. For the variables—tumor volume, stage and grade a multivariate analysis was performed to find the relationship between overall survival, local progression and metastasis. Toxicity was evaluated according to CTCAE scale version 4.ResultsAfter a median follow-up of 16 months, 23 patients (62%) achieved complete remission. The median time to local progression and metastasis was 7 months. Local control (LC) at 2 and 5-years was 70% and 62%, respectively. Progression-free survival (PFS) and overall survival (OS) were 57% and 49% at 2 years and 41% and 27% at 5 years, respectively. Statistical analysis revealed that larger tumors had worse overall survival and a greater chance of metastasis. Log-Rank GTV > 44 ccm (HR = 1.96; [95% CI (0.87; 4.38)]; p = 0.11). No boost-related severe acute toxicity was observed. Late osteonecrosis was observed in 3 patients (8%).ConclusionThe combination of EBRT and stereotactic hypofractionated boost is safe and seems to be an effective option for dose escalation in patients with advanced floor of the mouth tumors who are ineligible for surgical treatment and require a non-invasive approach.

Survival and Surgical Complications in Anaplastic Thyroid Cancer Patients After Completed Multimodal Treatment.

This study aimed to examine survival and surgical complications in patients with anaplastic thyroid cancer (ATC) after multimodal treatment. Since 2002, the recommended treatment strategy for ATC at our centre has been hyperfractionated accelerated radiotherapy (HART) with high doses to the neck (64 Gy), combined with weekly doxorubicin, and surgery after 4-8 weeks, if feasible. Between 2002 and 2014, 14 patients completed HART and thyroid surgery. Eight patients had preoperative HART, and six postoperative HART. Median survival was 20 months (range=4-110 months) in all patients, 51 months (range=4-110 months) and 18.5 months (range=9-56 months) in the preoperative and postoperative HART groups, respectively. Six patients survived for more than two years, and four patients survived for more than five years. Seven patients had postoperative complications. In this series of selected patients, an improved survival after aggressive, multimodal treatment was observed. Preoperative HART may promote survival although complications may be more frequent.

Neo-adjuvant chemotherapy followed by either continuous hyper-fractionated accelerated radiation therapy week-end less or conventional chemo-radiotherapy in locally advanced NSCLC-A randomised prospective single institute study.

Better locoregional control and increased overall survival by continuous hyper fractionated accelerated radiotherapy have been shown in unresectable nonsmall cell lung carcinoma (NSCLC). Dose escalation and neoadjuvant chemotherapy (NACT) along with continuous hyperfractionated accelerated radiotherapy week end-less (CHARTWEL) were also tried for improved survival. In this present study, we compared the results of NACT followed by CHARTWEL against NACT followed by conventional concurrent chemo-radiation therapy. The aim of this study is to compare the locoregional control and toxicities in NSCLC Stage IIIA and B in both arms. Randomized, prospective single-institutional study with a study population comprising all locally advanced unresectable NSCLC patients enrolled in 2014 at our institute. All enrolled patients were randomized into two arms-CHARTWEL and concomitant chemo-radiotherapy (CCRT), after three weeks of the fourth cycle of NACT. In CHARTWEL arm 30 patients received two-dimensional radiotherapy (RT) 58.5 Gy/39 fr/2.5 weeks while in CCRT arm 30 received 66 Gy/33 fr/6.5 weeks. Disease response was evaluated at 6 months and toxicity assessment during and after treatment completion. Data were analyzed using tools such as percentage, mean, Chi-square test and P value. Chi-square and P value was calculated by statistical online software (http://quantpsy.org). 28% of patients in study arm and 20% in control arm had complete response at 6 months after RT. Locoregional disease control was observed in 44% in study arm and 32% in control arm of patients. There was no statistical difference in grades of toxicities or overall survival (OS)/disease-free survival except persistent esophagitis Grade III seen in two patients of study arm. Study suggests that CHARTWEL in combination with NACT is an effective strategy to treat patients with locally advanced lung cancer with the advantage of a smaller dose and shorter duration. Although large multivariate studies still needed.

Accelerated hyperfractionated radiochemotherapy with temozolomide is equivalent to normofractionated radiochemotherapy in a retrospective analysis of patients with glioblastoma

BackgroundCurrent standard of treatment for newly diagnosed patients with glioblastoma (GBM) is surgical resection with adjuvant normofractionated radiotherapy (NFRT) combined with temozolomide (TMZ) chemotherapy. Hyperfractionated accelerated radiotherapy (HFRT) which was known as an option from randomized controlled trials before the temozolomide era has not been compared to the standard therapy in a randomized setting combined with TMZ.MethodsData of 152 patients with newly diagnosed GBM treated from 10/2004 until 7/2018 at a single tertiary care institution were extracted from a clinical database and retrospectively analyzed. Thirty-eight patients treated with NFRT of 60 Gy in 30 fractions (34 with simultaneous and 2 with sequential TMZ) were compared to 114 patients treated with HFRT of 54.0 Gy in 30 fraction of 1.8 Gy twice daily (109 with simultaneous and 3 with sequential TMZ). The association between treatment protocol and other variables with overall survival (OS) was assessed using univariable and multivariable Cox regression analysis; the latter was performed using variables selected by the LASSO method.ResultsMedian overall survival (OS) was 20.3 month for the entire cohort. For patients treated with NFRT median OS was 24.4 months compared to 18.5 months in patients treated with HFRT (p = 0.131). In univariable regression analysis the use of dexamethasone during radiotherapy had a significant negative impact on OS in both patient groups, HR 2.21 (95% CI 1.47–3.31, p = 0.0001). In multivariable analysis adjusted for O6-methylguanine-DNA methyl-transferase (MGMT) promotor methylation status, salvage treatment and secondary GBM, the use of dexamethasone was still a negative prognostic factor, HR 1.95 (95% CI 1.21–3.13, p = 0.006). Positive MGMT-methylation status and salvage treatment were highly significant positive prognostic factors. There was no strong association between treatment protocol and OS (p = 0.504).ConclusionsOur retrospective analysis supports the hypothesis of equivalence between HFRT and the standard protocol of treatment for GBM. For those patients who are willing to obtain the benefit of shortening the course of radiochemotherapy, HFRT may be an alternative with comparable efficacy although it was not yet tested in a large prospective randomized study against the current standard. The positive influence of salvage therapy and negative impact of concomitant use of corticosteroids should be addressed in future prospective trials. To confirm our results, we plan to perform a pooled analysis with other tertiary clinics in order to achieve better statistical reliability.

Dose–volume predictors of early esophageal toxicity in non-small cell lung cancer patients treated with accelerated-hyperfractionated radiotherapy

Background and purposeEarly radiation-induced esophageal toxicity (RIET) is one of the major side effects in patients with non-small cell lung cancer (NSCLC) and can be a reason for treatment interruptions. As the age of patients with NSCLC and corresponding comorbidities continue to increase, primary radiotherapy alone is a commonly used alternative treatment in these cases. The aim of the present study is to compare dosimetric and clinical parameters from the previously reported CHARTWEL trial for their ability to predict esophagitis and investigate potential differences in the accelerated and conventional fractionation arm. Material and methods146 patients of the Dresden cohort of the randomized phase III CHARTWEL trial were included in this post-hoc analysis. Side effects were prospectively scored weekly during the first 8 weeks from start of radiotherapy. To compare both treatment arms, recorded dose–volume parameters were adjusted for the different fractionation schedules. Logistic regression was performed to predict early RIET for the entire study group as well as for the individual treatment arms. Different dosimetric and clinical parameters were tested. ResultsPatients receiving the accelerated CHARTWEL schedule experienced earlier and more severe esophagitis (e.g. 20.5% vs. 9.6% ≥grade 2 at week 3, respectively). In contrast, the median time period for recovery of grade 1 esophagitis was significantly longer for patients with conventional fractionation compared to the CHARTWEL group (median [range]: 21 [12–49] days vs. 15 [7–84] days, p = 0.028).In univariable logistic regression none of the dose–volume parameters showed a significant correlation with early RIET grade ≥ 2 in the conventional irradiation group. In contrast, for patients receiving CHARTWEL, the physical dose–volumes parameters V40 and V50; and re-scaled values VEQD2,50 and VEQD2,60 were significant predictors of early RIET grade ≥ 2. Dose–volume parameters remained different between CHARTWEL and conventional fractionation even after biological rescaling. ConclusionOur results show a more dominant dose-volume effect in the CHARTWEL arm compared to conventional fractionation, especially for higher esophageal doses. These findings support the notion that dose–volume parameters for radiation esophagitis determined in a specific and time dependent setting of field arrangements can not be easily transferred to another setting. In clinical practice esophageal volumes receiving 40 Gy or more should be strictly limited in hyperfractionated-accelerated fraction schemes.

A prospective, multicenter DAHANCA study of hyperfractionated, accelerated radiotherapy for head and neck squamous cell carcinoma

Background: The study aimed to evaluate Hyperfractionated, Accelerated Radiotherapy (HART) with nimorazole for patients with head and neck squamous cell carcinoma (HNSCC) using loco-regional failure (LRF), overall survival (OS), early and late morbidity as endpoints.Material and methods: From February 2007 to January 2018, 295 patients with unresected HNSCC, T1-T4, N0-N3, M0, were treated with HART prescribed as 76 Gy in 56 fractions (fx), 10 fx weekly. IMRT was used in >90% of patients. No chemotherapy was given. Patients were prospectively registered in the DAHANCA database.Results: The median age was 64 years, 75% of patients were males. Primary sites were larynx (25%), pharynx (64%) and oral cavity (11%). In total, 59% were stage III-IV (UICC 2002). Of the 150 oropharyngeal cancer (OPC) patients, 42% were p16+. The proportion of patients receiving HART as planned was 97%. The median follow-up time was 66 months. Three-year actuarial LRF was 19% and OS was 66%. LRF was significantly higher for stage III–IV patients compared to stage I–II (25% vs. 11%, HR 2.12 [1.21–3.74]). The site-specific LRF rates were: for larynx 22% [12–32], hypopharynx 30% [16–45], non-p16+ oropharynx 15% [8–23], p16+ oropharynx 7% [1–13] and oral cavity 35% [18–53]. During therapy, 51% reported severe dysphagia and 60% required feeding tubes. The peak incidence of late, severe dysphagia and xerostomia was 21% and 9%, respectively. A comparison to historical data from previous DAHANCA trials showed that tumor control and morbidity are comparable to treatment with acceleration and/or chemo-radiation.Conclusions: HART represents an attractive approach for patients with HNSCC where treatment intensification is indicated.

PO-0738: Hyperfractionated-accelerated radiotherapy in locally advanced breast cancer: Fifteen-year results

PO-0738: Hyperfractionated-accelerated radiotherapy in locally advanced breast cancer: Fifteen-year results

Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase II study.

AIMTo evaluate the efficacy and tolerability of neoadjuvant hyperfractionated accelerated radiotherapy (HART) and concurrent chemotherapy in patients with locally advanced infraperitoneal rectal cancer.METHODSA total of 30 patients with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid radiotherapy and continuous infusion of 5-fluorouracil (325 mg/m2). All patients were operated 4-8 wk after neoadjuvant concomitant therapy.RESULTSIn the early phase of treatment, 6 patients had grade III-IV gastrointestinal toxicity, 2 patients had grade III-IV hematologic toxicity, and 1 patient had grade V toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had radiotherapy-related late side effects, i.e., grade IV tenesmus. Complete pathological response was achieved in 6 patients (21%), while near-complete pathological response was obtained in 9 (31%). After a median follow-up period of 60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and corresponding overall survival rates were 70% and 53.1%, respectively.CONCLUSIONAlthough it has excellent local control and complete pathological response rates, neoadjuvant HART concurrent chemotherapy appears to not be a feasible treatment regimen in locally advanced rectal cancer, having high perioperative complication and intolerable side effects. Effects of reduced 5-fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity may be examined in further studies.

Anaplastic thyroid cancer and hyperfractionated accelerated radiotherapy (HART) with and without surgery

Anaplastic carcinoma of the thyroid gland (ATC) is one of the most aggressive cancers in humans. With insufficient treatment, the disease most often leads to death in suffocation. From 2002, our treatment strategy has been hyperfractionated accelerated radiotherapy (HART) with high doses (64Gy) to the neck, followed by surgery 4-8weeks later if feasible, with the aim to gain control in the neck. After a pathology review, 51 patients were diagnosed with ATC in the period 2002-2014 in the south-east of Norway. Thirty-one received HART, and we present a study of these patients, with death in suffocation as the primary endpoint and survival as the second. No patients treated with HART died in suffocation. Six had a tracheostomy during their course of disease, of whom four were dependent on a tracheal cannula when they died. The best median survival, 19months, was obtained in the 13 patients where both radiotherapy and surgery were possible as primary treatments. Only surgery came out as a prognostic factor for survival in multivariate analysis. Patients surviving more than 2years were characterised by having surgery with R0 resection and no or small residual foci of ATC in the specimens. Stage 4C patients survived 3months only.

Hazard Model for Brain Metastases After Prophylactic Cranial Irradiation in Local Disease Small Cell Lung Cancer

Some patients with local-disease small cell lung cancer (LD-SCLC) still experience brain metastases (BM) even have received prophylactic cranial irradiation (PCI). We initiated this study to exploit risk factors for BM after PCI and develop harzard model to guide the clinical practice in LD-SCLC. LD-SCLC patients with PCI history from two institutions during 2003 and 2014 were retrospectively reviewed. BM free survival (BMFS), disease-free survival (DFS), extracranial disease-free survival (ECDFS), local recurrence-free survival (LRFS), and overall survival (OS) were estimated using Kaplan-Meier method. High risks and harzard model for BM were identified using univariate and multivariate Cox regression analyses. A total of 257 patients were eligible, among whom 47(18.3%) experienced BM at median follow-up of 34 months. In univariate analyses, performance status (PS) and thoracic radiotherapy schedule were associated with BM(P < 0.05). Multivariate analyses showed that worse PS (PS > 1),thoracic hyperfractionated accelerated radiotherapy (HART), longer start of any therapy to the end of radiotherapy(SER) were independent risks for BM and surgery was independent protective factor for BM (P < 0.05). Median LRFS, ECDFS, DFS and OS in the BM group were much shorter than the non-BM group(P < 0.05).In addition, elder than 60-yr, worse PS and PCI classification were independent risk factors for OS(P < 0.05). Surgery and thoracic radiotherapy biological effective dose (TRTBED) were independent protective factors for OS (P < 0.05). Worse PS, thoracic HART and longer SER were independent risks for BM after PCI in SCLC. Surgery decreased BM rate and improve OS. Prognosis was much worse in the BM group. Higher dose for PCI did not prolong BMFS but shortened OS. Further studies are needed to confirm our findings.

Radical chest wall resection and hyperfractionated accelerated radiotherapy for radiation-associated angiosarcoma of the breast: A safe and effective treatment strategy.

Radiation-associated angiosarcomas (RAS) of the breast are vascular tumors arising in a previous radiation field for primary breast cancer. They occur rarely but confer a high probability of local recurrence (LR) and poor prognosis. A wide range of treatment strategies exists due to limited evidence, and although resection is the definitive treatment, LR rates remain high. It has been suggested hyperfractionated accelerated radiotherapy (HART) has the potential to prevent LR. The sarcoma group at the Juravinski Cancer Centre (JCC) reports our experience of nine patients treated with radical resection and adjuvant HART. This is one of the largest reported cohorts we are aware of to receive this treatment. The JCC pathologic data base was reviewed between the year 2006-2015 for patients with RAS. Patients who received radical surgery and immediate HART were eligible. Patients underwent radical chest wall resection and en bloc mastectomy. Radiotherapy was then delivered to 4500 cGy in 45 fractions three times daily using parallel opposed photon beams and electron patching, or volumetric modulated arc therapy. Primary outcome was recurrence-free survival in months, and records were reviewed for descriptive reports of toxicity. We compared our results to other institutions experience with surgery alone or other adjuvant therapies. Median follow-up was 19 months (range 3-41 months). One of nine patients developed LR and developed metastasis, one died of other causes, and seven are alive with no recurrent disease. There were seven reports of mild skin toxicity during treatment. One patient developed chronic wound healing complications which eventually resolved and one patient developed asymptomatic radiation osteitis of a rib. On the basis of our experience at the JCC, we recommend treatment with radical chest wall resection and adjuvant HART to prevent recurrence in RAS patients. As demonstrated in our patients, the large normal tissue volume irradiated is tolerable with in combination with small fraction sizes, and no major toxicities were seen. Further investigation into adjuvant therapy regimens and prospective studies are required to reach consensus on optimal treatment for this disease.

Quality of life in long-term survivors treated for metastatic medulloblastoma with a hyperfractionated accelerated radiotherapy (HART) strategy.

An intensive therapeutic strategy for metastatic medulloblastoma was launched in 1998 in our Institution. The aim of this study was to examine the long-term quality of life (QoL) in survivor patients at least 3years after the end of the treatment. Patients were asked to complete self-administered QoL questionnaires. An index of physical impairment (IPI) was scored (range 0-100; the lower the score the better) based on clinical objective observations. Patients were divided into two groups (lower IPI group, and higher IPI group) and descriptively compared accordingly. The study was completed by 25/33 eligible patients. Despite patients with a higher IPI reported worse perceived health condition, they had better emotional and psychological scores than those with a lower IPI in all QoL questionnaires. In our sample, patients with more severe objective and perceived physical impairments reported a better psychosocial QoL, possibly because the greater attention paid to them by society and family contributes to a better adjustment in long-term survivors. On this base, it should be recommended that all survivors receive a strong support as the most impaired patients.

Impact of induction chemotherapy, hyperfractionated accelerated radiotherapy and high‐dose thiotepa on brain volume loss and functional status of children with primitive neuroectodermal tumour

The introduction of aggressive chemo-radiotherapy regimens has improved overall survival in children with primitive neuroectodermal tumours (PNET). However, these combinations may result in neurotoxicity. Previously reported magnetic resonance imaging abnormalities in children receiving intensive sequential chemotherapy, hyperfractionated accelerated radiotherapy (HART) and high-dose thiotepa prompted us to investigate the degree of brain volume loss and patients' functional status after therapy. We retrospectively reviewed clinico-radiological data of children with PNET treated in this way at our centre. We studied 14 children treated between December 2009 and April 2013. Data were not complete for one child. Performance status was severely restricted in four children, and mildly to moderately impaired in 7 of the 13 children. Eleven of 13 children showed mild-to-severe generalised neuroparenchymal atrophy, in 7 of whom neuroparenchymal volume loss was moderate to severe. Of these seven, six had received high-dose thiotepa. There was no correlation between brain volume loss and Lansky performance status. However, unexpected neurotoxicities, such as symptoms of transverse myelitis, were observed. Measurement of brain volume loss in patients treated with HART and high-dose thiotepa may not be sufficient to predict function. However, correlation of brain volume loss due to late neurotoxicity with performance decline may be more obvious over longer period of follow-up. The combination of HART and myeloablative courses of thiotepa is associated with severe neurotoxicity and subsequent decline in performance status in a significant proportion of patients.

1007P - Phase II-trial of concomitant hyperfractionated-accelerated radiotherapy (HART) with cisplatin (Cis) plus cetuximab (Cet) for locoregionally advanced inoperable squamous cell head and neck cancer: 5-year end results

1007P - Phase II-trial of concomitant hyperfractionated-accelerated radiotherapy (HART) with cisplatin (Cis) plus cetuximab (Cet) for locoregionally advanced inoperable squamous cell head and neck cancer: 5-year end results

Accelerated hyperfractionation plus temozolomide in glioblastoma.

IntroductionHyperfractionated (HFRT) or accelerated hyperfractionated radiotherapy (AHFRT) have been discussed as a potential treatment for glioblastoma based on a hypothesized reduction of late radiation injury and prevention of repopulation. HFRT and AHFRT have been examined extensively in the pre-Temozolomide era with inconclusive results. In this study we examined the role of accelerated hyperfractionation in the Temozolomide era.Materials and methodsSixty-four patients who underwent AHFRT (62 of which received Temozolomide) were compared to 67 patients who underwent normofractionated radiotherapy (NFRT) (64 of which received TMZ) between 02/2009 and 10/2014. Follow-up data were analyzed until 01/2015.ResultsMedian progression-free survival (PFS) was 6 months for the entire cohort. For patients treated with NFRT median PFS was 7 months, for patients treated with AHFRT median PFS was 6 months. Median overall survival (OS) was 13 months for all patients. For patients treated with NFRT median OS was 15 months, for patients treated with AHFRT median OS was 10 months. The fractionation regimen was not a predictor of PFS or OS in univariable- or multivariable analysis. There was no difference in acute toxicity profiles between the two treatment groups.ConclusionsUnivariable and multivariable analysis did not show significant differences between NFRT and AHFRT fractionation regimens in terms of PFS or OS. The benefits are immanent: the regimen does significantly shorten hospitalization time in a patient collective with highly impaired life expectancy. We propose that the role of AHFRT + TMZ should be further examined in future prospective trials.