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Small cell lung cancer (SCLC) accounts for approximately 20% of all lung cancers. The main treatment is chemotherapy (Ch). However, the addition of radiotherapy significantly improves overall survival (OS) in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to Ch. Prophylactic cranial irradiation reduces the risk of brain metastases and improves OS in both metastatic and non-metastatic patients. The 5-year OS rate in patients with limited-stage disease (non-metastatic) is slightly higher than 30%, but less than 5% in patients with extensive-stage disease (metastatic). The present clinical guidelines were developed by Spanish radiation oncologists on behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Society of Radiation Oncology to provide a current review of the diagnosis, planning, and treatment of SCLC. These guidelines emphasise treatment fields, radiation techniques, fractionation, concomitant treatment, and the optimal timing of Ch and radiotherapy. Finally, we discuss the main indications for reirradiation in local recurrence. Sin financiación No data 2021 UEM

INTRODUCTION Patients with high risk medulloblastoma are treated either with high dose chemotherapy or hyperfractionated radiotherapy. Both approaches are not feasible in resource-limited countries. POG9031 trial has reported favourable outcome for high risk medulloblastoma using standard chemotherapy and radiotherapy only. Hence, we have adopted the protocol using chemotherapy first approach due to logistical reasons. OBJECTIVE To review the outcome of children diagnosed with high risk medulloblastoma in Hospital Kuala Lumpur. METHODS Patients diagnosed with high risk medulloblastoma between January 2015 and June 2018 treated using the chemotherapy first approach as per POG9031 protocol were identified. Data was then extracted and analysed. RESULTS Nine patients were identified, 3 boys and 9 girls. Median age was 9.3 years (range 2.6 – 15.9 years). Median follow up for survivors are 3.6 years. Five patients (55.6%) had macroscopic metastatic disease at diagnosis. All patients had significant residual disease post-op. Only 3 patients are disease free till last follow up, giving a 3 years event free survival of 16%. Of the 6 patients who had relapsed, 4 have died, giving a 3 years overall survival of 46%. Patients with no metastasis at diagnosis (M0) fared better with 3 years event free survival of 38%, but 3 years event free survival for patients with macroscopic metastatic disease (M+) was 0%. CONCLUSION Outcome of children with high risk medulloblastoma treated with chemotherapy first approach was dismal.

Hyperfractionated radiation therapy has been established as a radical treatment for head and neck cancer. The radiobiological hypothesis for hyperfractionation has been derived from that of fractionated radiation therapy, and it enables us to improve therapeutic gain by delivering a small fraction dose at optimal interfraction intervals, i. e., 1) reduction of normal tissue complication while maintaining tumor control probability, 2)improvement of tumor control probability while maintaining the incidence of normal tissue complications within an acceptable level. The understanding of radiobiological hypothesis or theory is important in clinical application of hyperfractionation.

BACKGROUND To analyze the impact of weight loss before and during chemoradiation on survival outcomes in patients with locally advanced head and neck cancer. METHODS From 07/1994-07/2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiation therapy alone or the same radiation therapy combined with two cycles of concomitant cisplatin. The primary endpoint was time to any treatment failure (TTF); secondary endpoints were locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Patient weight was measured 6 months before treatment, at treatment start and treatment end. RESULTS The proportion of patients with >5% weight loss was 32% before, and 51% during treatment, and the proportion of patients with >10% weight loss was 12% before, and 17% during treatment. After a median follow-up of 9.5 years (range, 0.1 - 15.4 years) weight loss before treatment was associated with decreased TTF, LRRFS, DMFS, cancer specific survival and OS in a multivariable analysis. However, weight loss during treatment was not associated with survival outcomes. CONCLUSIONS Weight loss before and during chemoradiation was commonly observed. Weight loss before but not during treatment was associated with worse survival.

今回, 当院での下咽頭癌に対する多分割放射線治療初期成績を検討した。1996年～2000年12月までの間に多分割法で根治的放射線治療を施行した16例を対象とした。平均年齢65歳 (52～84), 性別は全例男性。病期分類はI期2例, II期5例, III期3例, IV期6例であった。病理組織型は全て扁平上皮癌であった。放射線治療は4MVX線にて1.2Gy/fr, 2fr/dayで, 咽頭ならびに頸部に照射し, shrinking field 法を用いて平均総線量72Gy (66～79.2) 施行した。照射終了時点での下咽頭局所の照射効果はCR 13例 (81.3%), PR 3例 (18.7%) であった。2年生存率, 2年局所制御率はそれぞれ69.9%, 63.6%であった。今回の検討では, 多分割法による下咽頭癌の治療成績は比較的良好であり, 有用な治療法となる可能性が示唆された。

Background A regimen of multi-drug chemotherapy alternating with split course hyperfractionated radiation therapy (HFRT) was adopted for the treatment of patients with rhabdomyosarcoma (RMS). The purpose of this treatment regimen was to allow for the timely delivery of radiation and chemotherapy, reduce treatment-related toxicity, and improve compliance. Procedure. Forty-four patients with stages II-IV RMS were treated with HFRT and received 5,400 cGy. The treatment was administered in two courses (3,000 and 2,400 cGy) and separated by a 4-week interval. HFRT consisted of 150 cGy delivered twice a day, 5 days a week with an interfraction interval of 4–6 hours. A limited comparison was made between the HFRT patients and 42 historical patients with comparable clinical characteristics who were treated with similar chemotherapy and conventionally fractionated radiation therapy (CFRT) (median 4,800 cGy, range 4,000–5,680 cGy). Results. HFRT patients completed radiation therapy in 59.1 ± 9.4 days (mean ± SD) and CFRT patients completed treatment in 56.6 ± 10.5 days compared to an expected 52 and 40 days, respectively. With a median follow-up of 55 months for the HFRT patients and 104 months for the CFRT patients, no differences in local control or survival were noted. Nine of 44 (21%) HFRT and 8/42 (19%) CFRT patients experienced local failure. The median time to local failure was 15 months for patients in the HFRT group and 11 months for patients in the CFRT group. Conclusions. The results of the HFRT regimen were acceptable in terms of toxicity and compliance. No improvement in local control was obtained by alternating radiation and chemotherapy. The lack of difference between patients treated with HFRT and CFRT may be related to the lengthened treatment time of the split course regimen, the small difference in total dose, and tumor repopulation. Med. Pediatr. Oncol. 30:332–338, 1998. © 1998 Wiley-Liss, Inc.

Sinonasal undifferentiated carcinoma (SNUC) is a rare and highly aggressive neoplasm of the paranasal sinuses, which has recently been characterized as a distinct pathologic entity. The prognosis for patients with SNUC is poor. Early case reports describe patients with lesions that were clinically advanced at initial presentation and surgically unresectable. Survival was reported in months after treatment with chemotherapy and radiation. As more experience was gained with treatment of SNUC, it was found that aggressive, combined surgical therapy of lesions previously considered unresectable has shown increased survival. We report a case of a 38-year-old man with SNUC originating in the posterior ethmoid, extending into the anterior cranial fossa and orbit, who was treated with preoperative hyperfractionated radiation therapy, chemotherapy, and craniofacial resection.

Background. Most children with brain stem gliomas (BSG) die within 18 months of diagnosis. Early experience suggested that hyperfractionated radiation therapy (RT) at a dose of 72 Gy, administered in 1-Gy fractions twice daily, possibly improved disease-free survival for children with BSG. Methods. To better characterize the toxicity and possible efficacy of this dose and fractionation of RT, 53 assessable children with diffuse intrinsic or malignant BSG were treated. Survival figures also were combined with outcome in 36 patients treated in a previous pilot study. Results. An objective response to treatment was observed in 28 of 53 (53%) patients; a partial response occurred in 7. No child died of treatment-related brain necrosis, although 7 of 53 did have intralesional cystic/necrotic changes within 6 weeks of completion of RT. The overall survival rate for patients in the study was 38% (± 6.5) at 1 year, 14% (± 5.4) at 2 years, and 8% (± 6.5) at 3 years. Leptomeningeal dissemination was observed in 4 of 48 (8%) children who had relapses. A greater than 2-month duration of symptoms before diagnosis was related to a better prognosis. There was no statistical association between any other clinical parameter, neuroradiographic finding, or pathologic finding and outcome. Combined with that in 35 patients treated in the pilot study, the survival rate in 88 children was 14% (k 5) at 3 years. Conclusions. The radiographic response rate is encouraging; however, it cannot be concluded that hyperfractionated RT, at this dose schedule and total dose, is superior to conventional RT. Cancer 1993; 72:1414-21.

Damage to the lumbosacral plexus is an infrequent complication of radiation therapy to pelvic or spinal lesions. Described is a case of neurologic injury presenting in a young man treated definitively for a paraspinal soft tissue sarcoma. Neurologic symptoms and signs were limited to lower motor neuron deficits without sensory or sphincter disturbances. There remains no evidence of recurrence of the primary lesion. This is the first reported case of lumbosacral plexopathy occurring after a course of hyperfractionated radiotherapy. © 1993 Wiley-Liss, Inc1 .

Hyperfractionated radiation therapy (HFX) attempts to overcome tumor proliferation during treatment by permitting higher total doses in the same overall time as standard fractionation. Whereas interruptions, including splits, reduce local control with standard fractionation in carcinoma of the upper respiratory and digestive tracts, HFX might compensate for interruptions. Patients were randomized to receive total doses of 6720, 7200, 7680, and 8160 cGy, using 120 cGy twice daily, 5 days per week. Those analyzed received +/- 4% of assigned total dose and lived 90 days or more. Treatment was completed within 5 days of the time specified for each treatment arm in 233 patients; 48, 80, and 131 patients had delays 14, 10, and 5 days or more, respectively. Locoregional control and survival were significantly (P less than or equal to 0.03) reduced with delays of 5 days or more when corrected for prognostic factors. Late effects of radiation therapy were not affected by interruptions. These data support the hypothesis that proliferation (possibly accelerated) of tumor clonogens during treatment influences the outcome.

In this preliminary trial we studied 29 patients with primary malignant glial tumors to investigate the effectiveness of cisplatin combined with etoposide on these tumors. Hyperfractionated radiation therapy was given in the course of chemotherapy. The time to tumor progression in these glioblastoma multiforme (GBM) patients encouraged us to continue this treatment in a phase III study.

A prospective, randomized Phase I late /II trial of hyperfractionated radiation therapy was conducted: 1.2 Gy minimum tumor dose was administered twice daily with a minimum interval of 4 hr, 5 days per week. Patients with Stage III and IV carcinomas of the oral cavity, oropharynx, nasopharynx, hypopharynx, and supraglottic larynx were stratified by site, presence or absence of nodal metastases, and performance status. They were assigned to four total doses between 67.2 Gy and 81.6 Gy to all known tumors. The highest dose arm was opened after preliminary assessment indicated acceptable late morbidity rates with the three lower doses. Of 479 patients entered, 260 patients were randomized to the three lower total doses and 237 were analyzed for this preliminary report: 63 were assigned to receive 67.2 Gy, 58 to 72.0 Gy, and 116 to 76.8 Gy. Estimates of grade 4 necrosis at 2 years were 10.0%, 5.1%, and 13.9%, respectively, for patients who received total doses of 67.2 Gy, 72.0 Gy, and 76.8 Gy. There was a suggestion of a trend toward increased local control at 24 months (Kaplan-Meier estimates of 25% for 67.2 Gy, 37% for 72.0 Gy, and 42% for 76.8 Gy) ( p = .08). No difference was observed in survival. Assessment of the results using Cox regression models to correct for slight inequalities of pretreatment prognostic variables supported a total dose-tumor control relationship ( p = .054). Results for the lowest dose arm were comparable to previous RTOG studies of common fractionation with similar total doses. The higher local control rates with 72.0 and 76.8 Gy using hyperfractionated radiation therapy suggest an improvement in outcome with radiation therapy for advanced carcinomas of the upper aerodigestive tracts. These preliminary findings have led to a Phase III comparison of hyperfractionated radiation therapy with 1.2 Gy b.i.d. with standard fractionation.

SUMMARY A rare case of frontal sinus carcinoma is reported. The patient developed early recurrence following surgery, and was managed by accelerated hyperfractionated radiation therapy and concurrent cisplatinum-based systemic chemotherapy. The patient has remained disease-free for 30 months following the end of treatment.

Background: Hyperfractionated radiation therapy is recognized to be a better treatment method, especially regarding local control, than conventional radiation therapy for oropharyngeal carcinoma. However, the survival benefit of hyperfractionated radiation therapy for oropharyngeal carcinoma has not been reported so far. Moreover, patient populations of previous studies were mostly white or African-American, and rarely included Orientals. Thus, the current study is designed to evaluate not only local control but the survival benefit of hyperfractionated radiation therapy for oropharyngeal carcinoma in a Japanese population. Methods: The eligibility criteria were as follows. The patients were 20 years or older. Performance status ranged from 0 to 2. No patient with double carcinoma was included except those with superficial esophageal carcinoma or advanced carcinoma controlled for at least 2 years after treatment. In our radiation protocol, hyperfractionated radiation therapy was adopted using 1.2 Gy per fraction, two fractions per day (6 h apart), 5 days a week, for a total dose of 66 Gy or more. Results: Complete response was achieved in all 14 patients with oropharyngeal lesions. In five patients with lymph node metastasis, complete response was achieved in four patients and partial response was achieved in the remaining one. The 3-year loco-regional control rate was 77% and the 3-year overall survival rate was 69%. Conclusions: Treatment with hyperfractionated radiation therapy is considered superior to conventional radiation therapy with acceptable toxicity for Japanese patients with oropharyngeal carcinoma in terms of loco-regional control rate and overall survival rate.

e17044 Background: This is an update of a randomized study comparing the use of cetuximab versus platinum based chemotherapy with concurrent hyperfractionated radiation therapy (HRT) in locally adv...

A lthough control and cure rates for early cancer of the head and neck are good, advanced, unresectable lesions in these sites remain a therapeutic problem, l Induction or adjuvant chemotherapy, alone or in conjunction with conventional irradiation, has not resulted in great improvement] While hyperfractionated radiation therapy regimens have offered some gain in response and local control, toxicity is frequently great. 3'4 At the University of Miami, we have pursued treatment strategies for these tumors that seek to combine effective chemotherapeutic regimens with innovative and more rational approaches to irradiation. In particular, we have sought to exploit the dynamic nature of the various factors governing growth of tumors and normal tissues.

We designed a phase II trial to examine the benefit of preoperative hyperfractionated radiation therapy (XRT) and concurrent chemotherapy for patients with locally advanced esophageal cancer (LAEC).The pathologic complete response (pCR) was the primary endpoint to estimate efficacy.Twenty-three patients with LAEC received twice-daily XRT during wk 1 and 5 and once-daily XRT during wk 2-4 (59 Gy). Cisplatin (100 mg/m(2)) was given on d 1, while 5-fluorouracil (1000 mg/m(2)) was given by continuous infusion the first and fifth weeks of the XRT.The pCR for the 19 patients undergoing esophagectomy was 16%. The study was closed at the interim analysis having not met the required minimum pCR rate of 20%. Hematologic toxicities consisted of grades III and IV neutropenia observed in 33% and 14% of patients, respectively. Grade III nausea and vomiting was seen in 38% of patients. One grade V pulmonary toxicity occurred. The median survival was 44.6 mo with 65% of patients alive at 2 yr.The pCR rate in this trial did not meet the predetermined statistical minimum. With the encouraging 2-yr survival, it is not clear that pCR is a reliable surrogate endpoint to discern treatment efficacy.

Hyperfractionated radiation therapy (HF) is one of the most promising modifications of conventional fractionation (CF). However, two recent reviews on the efficacy of HF reached opposite conclusions: Stuschke and Thames (Int. J. Radiat. Oncol. Biol. Phys. 37: 259-267, 1997) concluded that the effectiveness of radiotherapy is consistently higher for HF than for CF, whereas Beck-Bornholdt et al. (Radiother. Oncol. 43: 1-21, 1997) concluded that evidence for a consistent therapeutic gain from HF is lacking and it cannot be ruled out that HF in head and neck tumors is detrimental. To clarify this issue, some important discrepancies between the two reviews are highlighted and a second look is taken at the clinical data published on HF in head and neck cancer. The most convincing prospective study so far is the EORTC trial 22791. This trial supports that HF allows escalation of the biologically effective dose to the tumor without a significant increase in late complications.

e16002 Background: This is a randomized study to compare the use of cetuximab versus platinum based chemotherapy with concurrent hyperfractionated radiation therapy (HRT). Acute and late morbidity, locoregional control (LC) and disease free survival (DFS) were set as primary end points, while overall survival (OS) was set as secondary end point. Methods: Between December 2009 and May 2011, 24 patients were randomly assigned to HRT consisting of 120 cGy twice daily, for a total of 69.6 Gys in 58 fractions over 6 weeks, plus either cisplatin chemotherapy at weeks 1, 4, 6 (Arm A: 14 patients) or weekly cetuximab (Arm B: 10 patients). The overall radiation dose was the same for the two groups. The median follow up time of the whole group was 14.07 months (IQR: 5.8- 25.0 ms). Results: Overall treatment time was 72 days in arm A and 63 days in arm B (p= 0.64). Grade 3 skin toxicity was experienced in 42.9% of patients in arm A and 9.1% in arm B (p= 0.09). Grade 3 mucositis was 64.3% in arm A and 45.5% in arm B (p= 0.43). Hematologic toxicity of G3-4 occurred in 21.4% and 18% of the cases respectively (p= 0.06). The mean percent of weight loss was (13 % +/- 0.1%) in group A, and (10.75 % +/- 0.1%) in group B respectively (p=0.56). Complete response was observed in 12 (85.7%) and 100% of patients of arm A and B respectively. Partial response was achieved in the remaining 2 (14.2%) patients in arm A. Loco-regional recurrence occurred in 2 (14.2%) of the patients in arm A after partial response, and one of them died eventually due to progressive disease. Two patients developed distant metastasis, one patient in arm A and another one in arm B. As the sample size was small and events were limited, survival analysis could not be computed at this stage of the study Conclusions: Hyperfractionated radiotherapy and concurrent cetuximab seems to have less side effects compared to concurrent platinum. There's a trend of less skin, mucosal and haematological toxicity with cetuximab that might become significant as the number of patients increase. We will be able to evaluate the outcomes of the patients regarding LC, DFS and OS within 2 years.

Squamous cell carcinomas of the oropharynx are among the sites within the upper aerodigestive tract most consistently treated with radiation therapy. The ability to observe directly the response to radiation therapy and to document local-regional control and failure result in their being excellent sites to investigate modifiers of radiation effects.

5566 Background: Extensive clinical research aimed at improving locoregional tumor control as well as functional outcome of patients with locally advanced head and neck cancer, using altered radiat...

RTOG Protocol 81-08, a feasibility study of hyperfractionated radiation therapy (HFX) with 1.2 Gy twice daily separated by 4-6 hours for non-small-cell cancer of the lung (NSCCL), was completed in 1983. Encouraging short-term results in a recently closed trial of HFX for NSCCL (RTOG 83-11) led to assessment of long-term outcome in the earlier trial. Of 120 evaluable patients who were assigned to total doses from 50.4 Gy to 74.4 Gy, all 5 of the 5-year survivors came from the 79 patients assigned to receive 69.6 Gy. The 5-year survival rates for the 79 patients were 14.3 +/- 9.4% for clinical RTOG Stage II, 5.9 +/- 4.0% for Stage III, and 3.2 +/- 3.2% for Stage IV. Combined Stage II and III 5-year survival rates were 8.3 +/- 4.0% for HFX 69.6 Gy compared to 5.6 +/- 1.5% for standard once-a-day irradiation in concurrent RTOG trials.