Accelerated Hyperfractionation Research Articles

Clinical Outcomes of Radiotherapy for Stage 1 Glottic Carcinoma: Comparing Accelerated Hyperfractionation and Once-daily Fractionation.

Accelerated hyperfractionation (AHF) is used in head and neck cancer to improve the local control (LC) rate, but reports of outcomes for early-stage GC are limited. The outcomes of radiotherapy (RT) for stage 1 glottic carcinoma (GC) were retrospectively analyzed, comparing AHF and once-daily fractionation (ODF) using 2.0-2.4 Gy. A total of 102 patients with stage 1 GC underwent RT alone between 2007 and 2021, with 43 in the AHF group and 59 in the ODF group. A p-value less than 0.05 was considered to indicate a significant difference. The 5-year LC rate was 98% in the AHF group and 91% in the ODF group (p=0.19). During RT, significantly more patients in the AHF group required opioids due to mucositis than in the ODF group (74% vs. 25%, p<0.001), and the rate of aspiration pneumonia tended to be higher in the AHF group than in the ODF group (7% vs. 0%, p=0.072). There was no difference in the LC rate between AHF and ODF for stage 1 GC. Moreover, the AHF group required opioids at a higher rate and tended to have a higher risk of developing aspiration pneumonia.

A Randomized Prospective Study of Concurrent Chemo-Radiotherapy vs Accelerated Hyperfractionation in Advanced Cancer of Head and Neck.

Locally advanced unresectable squamous cell carcinoma of head and neck has poor locoregional control when treated with conventionally fractionated Radiation Therapy (RT) alone. However, Concurrent Chemo-Radiotherapy (CRT) and altered fractionated RT schedules like Accelerated Hyperfractionation (AHF) are two different treatment strategies that have shown to be associated with better efficacy as compared to conventional RT alone in such cases. Aim of the study was to compare these two treatment strategies i.e., CRT and AHF radiation treatment to know which is better in terms of clinical outcome and toxicity in patients of locally advanced unresectable squamous cell carcinoma of head and neck. A prospective randomized trial was done to compare the effect of CRT and of AHF radiation treatment in locally advanced unresectable head and neck cancer on 15 patients in each arm and followed up over three months period. At the end of three months after completion of treatment protocol, complete response was 62% in CRT arm and 53% in AHF arm. In CRT arm and AHF arm, Grade 3 skin reactions were observed in 100% and 87%, grade 3 mucosal reactions were in 62% and 67% of cases, respectively. Three patients died in CRT arm (two due to myelosuppression and associated infection; one during the treatment and another after two weeks of treatment completion. The third patient expired after one month of treatment completion at his native place due to unknown reason). One patient died in AHF arm (during treatment due to cardiac event). Efficacy of AHF was comparable to CRT with lesser toxicity. So the present study suggests that AHF should be preferred over CRT in locally advanced, unresectable, squamous cell head and neck cancer followed over three months non-treatment period.

Dose-escalation study of chemoradiotherapy with use of involved-field conformal radiotherapy and accelerated hyperfractionation for stage III non-small cell lung cancer.

7564 Background: To determine a recommended dose (RD) of chemoradiotherapy with use of involved-field conformal radiotherapy and accelerated hyperfractionation (AHF) for stage III non-small cell lung cancer (NSCLC). Methods: Eligible patients had unresectable stage III NSCLC, age of less than 75 years, PS: 0 or 1, V20 of 35% or less. PET was used for staging. Cisplatin (80mg/m2) was administered on day 1 and vinorelbine (20mg/m2) was administered on days 1 and 8 for two cycle. Twice-daily radiation therapy (1.5 Gy per fraction) without elective nodal irradiation started on day 1. Total doses were 60Gy in 40 fractions and 66Gy in 44 fractions at levels 1 and 2 respectively. After concurrent chemoradiotherapy, consolidation chemotherapy regimen was cisplatin (80mg/m2) on day 1 and vinorelbine (20mg/m2) on days 1 and 8 every 4 week for three cycles. The dose-limiting toxicity (DLT) was defined as grade ≥ 3 esophagitis, grade 3 neutropenic fever, grade ≥ 3 other non-hematologic toxicities and interruption of irradiation for more than 2 weeks. DLT was monitored for 90 days. Results: A total of 12 patients were enrolled (6 patients in Level 1, 6 patients in Levels 2). DLTs were noted in 2 patients at Level 1, which were grade 3 esophagitis and grade 3 febrile neutropenia. Radiation dose was escalated up to 66 Gy in 44 fractions (Level 2), and there was no DLT. In principle, Sixty-six Gy in 44 fractions (Level 2) should be the RD. Major toxicities were leucopenia, neutropenia, and anemia. The response rate, the median progression free survival time, and the median overall survival time was 83.3%, 10.4 months, and 36.3 months for all patients, respectively. Conclusions: The RD was 66 Gy in 44 fractions (Level 2). The toxicity of this chemoradiothrapy regimen was manageable and efficacy is promising. The efficacy and safety of this regimen should be confirmed in a phase II study. Clinical trial information: UMIN000003769.

Accelerated hyperfractionated radiotherapy within trimodality therapy concepts for stage IIIA/B non-small cell lung cancer: Markedly higher rate of pathologic complete remissions than with conventional fractionation

BackgroundRadiation dose escalation within definitive radiochemotherapy (RTx/CTx) was not successful for stage III non-small cell lung cancer (NSCLC) using conventional fractionation (CF). Accelerated-hyperfractionation (AHF) counteracts tumour cell repopulation. In this observational study, the effects of neoadjuvant RTx/CTx using AHF or CF were studied by histopathology and using the survival end-point. MethodsData from all consecutive lung cancer patients treated with neoadjuvant RTx/CTx and thoracotomy between 08/2000 and 06/2012 were analysed. Patients received induction chemotherapy (cisplatin-doublets) followed by concurrent RTx/CTx using AHF (45Gy/1.5Gy bid) or CF-RTx (46Gy/2Gy qd). For estimating the AHF versus CF treatment effects, multivariate analysis (MA), propensity score weighting (PS), and instrumental variable analysis (IV) were used. Findings239 patients were treated, median age 58 (34–78)years, stage II/IIIA/B: 19/88/132, squamous cell/adenocarcinomas/other: 98/107/34; AHF/CF-RTx 112/127 patients. No significant differences between both groups, in tumour related factors (age, gender, Charlson comorbiditiy score, lactate dehydrogenase (LDH), haemoglobin, stage, histopathology and grading), existed. Crude rates of pathologic complete responses (pCR) in AHF and CF groups were 37% and 24% respectively. The dose fractionation effect on pCR was significant (p⩽0·006, PS and IV analyses). There was a significant dependence of pCR on biologically effective dose. pCR also depended on treatment time (MA, p=0·04; PS, p=0·0004). Median treatment time was 22 d or 31 d using AHF or CF (p<0.0001), respectively. Adenocarcinomas had lower pCR rates in comparison to other histologies. Five-year survival of patients with pCR was 65%, independent of the fractionation. InterpretationThis large monoinstitutional analysis demonstrates an increased effect of AHF on pCR of lung cancer which modifies overall survival.

Accelerated Hyperfractionated Radiation Therapy Within Trimodality Therapy Concepts for Stage IIIa/b Non-small Cell Lung Cancer: Markedly Higher Rate of Pathologic Complete Remissions Than With Conventionally Fractionated Radiochemotherapy

Pathologic complete remission (pCR) after neoadjuvant radiochemotherapy (RTx/CTx) is related to long-term survival for stage III non-small cell lung cancer (NSCLC) patients and is a surrogate marker for local effectiveness. Repopulation is a problem for fast growing tumors and accelerated-hyperfractionation (AHF) has been proven to be superior in SCLC. For NSCLC, data are missing up to now that demonstrate progress over conventionally fractionated (CF) RTx/CTx to lead a way for further treatment optimization.

Dose-escalation study of chemoradiotherapy of three-dimensional conformal radiotherapy (3D-CRT) with accelerated hyperfractionation (AHF) and concurrent chemotherapy (cisplatin and vinorelbine) for unresectable stage III non-small cell lung cancer (NSCLC).

e17518 Background: To determine a recommended dose (RD) of radiotherapy using AHF for unresectable NSCLC. Methods: Eligible patients had unresectable stage III NSCLC, age of less than 75 years, PS: 0 or 1, V20 of 35% or less. PET was used for staging. Cisplatin (80mg/m2) was administered on day 1 and vinorelbine (20mg/m2) was administered on days 1 and 8 for first cycle. Twice-daily 3D-CRT (1.5 Gy per fraction) without elective nodal irradiation started on day 1. Total doses were 60 Gy in 40 fractions and 66 Gy in 44 fractions at levels 1 and 2 respectively. After concurrent chemoradiotherapy, consolidation chemotherapy regimen was cisplatin (80mg/m2) on day 1 and vinorelbine (20mg/m2) on days 1 and 8 every 4 week for three cycles. The dose-limiting toxicity (DLT) was defined as grade ≥a3 esophagitis, grade 3 neutropenic fever, grade ≥a3 other non-hematologic toxicities and interruption of irradiation for more than 2 weeks. DLT was monitored for 90 days. Results: A total of 12 patients were enrolled (n=6,4 in the levels 1,2). DLTs were noted in 2 patients at Level 1,which were grade 3 esophagitis and the other grade 3 febrile neutropenia. Radiation dose was escalated up to 66 Gy in 44 fractions (Level 2), and there was no DLT in level 2. In principle, Sixty-six Gy in 44 fractions (Level 2) should be the RD. Major toxicities were leucopenia, neutropenia, and anemia. The response rate (RR) and 1-year survival rate was 83.3% and 91.7%, respectively. The progression free survival time was 11.3 months. Conclusions: The RD was 66 Gy in 44 fractions (Level 2). The toxicity of this chemoradiothrapy regimen was managiable and efficacy is promissing. Phase II study is warranted.

A Phase I Study of Chemoradiotherapy with Use of Three-dimensional Conformal Radiotherapy (3D-CRT) and Accelerated Hyperfractionation (AHF) for Unresectable Non-small Cell Lung Cancer (NSCLC): WJOG3305

A Phase I Study of Chemoradiotherapy with Use of Three-dimensional Conformal Radiotherapy (3D-CRT) and Accelerated Hyperfractionation (AHF) for Unresectable Non-small Cell Lung Cancer (NSCLC): WJOG3305

The Impact of Radiation Dose and Fractionation on Outcomes for Limited-Stage Small-Cell Lung Cancer

To review the treatment outcomes of limited-stage small-cell lung cancer (LS-SCLC) patients and to compare the outcomes among three groups in which the total radiation doses were 45 Gy with accelerated hyperfractionation (AHF), <54 Gy with standard fractionation (SF), and > or =54 Gy with SF. LS-SCLC patients that had been treated with chemoradiotherapy between 1997 and 2007 at Aichi Cancer Center Hospital were reviewed in this study. Of the 127 eligible patients, there were 37 patients in the AHF group, 29 in the SF <54 Gy group, and 61 in the SF > or =54 Gy group. Fifty-five patients (43%) were alive at the time of this analysis, and the median follow-up time of the surviving patients was 33 months. The median survival times were 30.0 months (95% confidence interval [CI] 16.3-43.7) for the AHF group, 14.0 months (CI 6.6-21.4) for the SF <54 Gy group, and 41.0 months (CI 33.9-48.1) for the SF > or = 54 Gy group. As for the local control rates, and the overall and progression-free survival rates, all outcomes were significantly lower in the SF <54 Gy group than in the other two groups, although no significant difference was found between the AHF and SF >/=54 Gy groups. These results suggest the importance of a high dose of radiation when using once-daily regimen. This study will support future prospective studies to establish optimal radiation doses and fractionation.

Early clinical outcomes of 3D-conformal radiotherapy using accelerated hyperfractionation without intracavitary brachytherapy for cervical cancer

To evaluate the outcome of cervical cancer patients unable to undergo conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal radiotherapy (3DCRT) alone using accelerated hyperfractionation (AHF). We reviewed the records of 7 patients who had received definitive radiotherapy with 3DCRT alone using AHF for cervical cancer between 2002 and 2005. FIGO stage was IB (1), IIB (2), IIIA (1), IIIB (2), and IVA (1). The reason we did not perform ICBT was due to patient refusal. In 1 patient with stage IB, a total dose of 65.4 Gy was delivered by local irradiation (LI) only. In 1 patient with stage IIIA, a total dose of 60 Gy was delivered by LI only. In 5 patients with Stage IIB-IV, a median total dose of 70.8 Gy was delivered by combination of whole pelvic irradiation (median dose of 45 Gy) with LI. Median overall treatment time was 42 days. Median follow-up for survival patients was 17 months. Out of 7 patients, 6 patients had CR and 1 patient had PR. The response rate was 100%. The 2-year local control rate was 85.7%. Of these patients, 5 are alive without disease and 1 is alive with lung metastasis. Our outcomes suggest that 3DCRT using AHF may be a promising as a definitive treatment for cervical cancer when ICBT is not able to be performed.

E-33. Prevention and management of brain metatsases

Between 25%30%% of all patients with lung cancer develop brain metastases at some stage of their life and this percentage is likely to increase with lengthening survival and more aggressive multi-modality treatment of patients with advanced stage of disease at presentation [l]. Until recently brain metastases were considered to be a terminal event and their treatment was essentially palliative. With increasing frequency of failure in the brain together with development of new techniques and reports of prolonged survival after aggressive treatment we need to reassess our approach to patients with brain metastases and develop new treatment algorithms to ensure that they receive the optimal therapy. This should not only maximise their opportunity for survival but also provide functional improvements and improved quality of life. The initial evaluation of lung cancer patients with neurological symptoms requires confirmation of diagnosis and assessment of prognostic factors that will determine the optimal approach to treatment. Radiological evaluation with CT and in patients with apparently solitary lesion MRI confirms the diagnosis and establishes the extent of involvement. This is important as solitary lesions have a different prognosis to multiple tumours or patients with wider dissemination through the CSF pathways Steroids to control peri-tumoral oedema and anticonvulsants in patients with seizures provide immediate palliation and allows time for decisions on further therapy. Number of studies confirmed that solitary metastases, time of their appearance (synchronous/metachronous), presence of active tumour at other sites, PS, functional neurological status and age of the patients are significant prognostic factors. Using recursivepartitioning models such as the RTOG [2] one can pick individual patients who fall into a favourable prognostic group. Radiation therapy to the whole brain (WBRT) is the mainstay of treatment for the majority of patients. For those in favourable prognostic category consideration should be given to additional ways of enhancing local control in the brain either by resecting [3] the solitary metastasis or stereotactically delivered radiation boost [4]. Both methods can improve rates of local response and prolong time to relapse at this site. Which one to choose will depend on the accessibility of the lesion, need for and value of fast internal decompression and availability of surgical expertise. Evidence suggests comparable results in expert hands, although surgery achieves faster response at a cost of higher immediate morbidity. The disruption of blood brain barrier by metatstatic disease enables access of many chemotherapy agents and in the presence of metatsatic disease at other sites this is a logical option. The prediction of response in the brain can be determined by sensitivity rules applicable to primary tumour. There is evidence that addition of WBRT improves rates and prolongs local control without influencing survival [5]. Most of lung cancer patients develop brain metastases in the context of advanced extra-cranial disease and fall in the poor prognostic category. The aims of treatment are palliative and role of radiotherapy or chemotherapy, particularly when accompanied by significant toxicity, is much less clear. Increasing radiation dose does not improve survival and may be detrimental to quality of life. Utility of currently available chemotherapy is limited by low response rates and significant toxicity of treatment. Studies assessing neurological function and quality of life have consistently demonstrated poor symptom control and low and rapidly deteriorating functional status despite treatment in most patients. Can we do better? Increasing the biological radiation dose using accelerated hyper fractionation schedules has not improved survival when compared to conventional radiotherapy in a randomised trial of good prognosis patients [6]. Is prevention the way forward? The ability of prophylactic cranial irradiation (PCI) to significantly reduce rates of brain relapse and improve survival has been convincingly demonstrated in small cell lung cancer (SCLC) [7]. Can this be replicated for patients with other histological types and can we identify a group most likely to benejit? Proposals to test this have been regularly raised over the last decade and promising results observed in exploratory studies. The lessons learned from the PC1 experience in SCLC should make progress faster than it has been so far and groups investigating multimodality treatment approaches should come together to run simple pragmatic randomised trials to evaluate the effectiveness of this approach. Until we have these results PC1 remains experimental and the group of lung cancer patients at risk of relapse in the brain is increasing. For majority of these the currently available therapy produces disappointing results.

The radiation oncologist's perspective on stereotactic radiosurgery.

Unfavorable gliomas: The basis for single-fraction stereotactic radiosurgery (SRS) is largely historical in nature and rooted in conventional thinking. This is derived from the original use of SRS in the treatment of arteriovenous malformations (AVMs), where the benefit of single-fraction high-dose radiation is clearly optimal in terms of addressing AVM obliteration kinetics. However, tumor cell kinetics are not the same as AVM obliteration kinetics and therefore may not be optimally addressed by single-fraction SRS. In addition, fractionated (F) SRS, as compared to single-fraction SRS, should allow for sparing of normal tissue damage. The relatively noninvasive nature of SRS allows for the potential of exploiting the use of FSRS and also allows for consideration of delivering FSRS in a split-course fashion. This provides an additional advantage over what can normally be achieved by use of stereotactic brachytherapy, in that sterotactic brachytherapy is likely to be performed only once in the course of a patient's primary treatment. This strategy exploits tumor and/or normal tissue cell kinetics, inclusive of attempting to counteract the initial accelerated tumor growth phase pre-CEBRT(conventional external beam radiation therapy), thereby decreasing the rate of clinical tumor progression during CEBRT. This split-course design should also help to counteract the effect of accelerated tumor repopulation post-CEBRT. Our unique experience with this approach in patients with unfavorable gliomas will be reviewed. Brain metastases: While whole brain radiation therapy (WBRT) remains a standard of care in patients with brain metastases, is potential neurocognitive morbidity remains a poorly understood concern. Despite this, and with an increasing role of surgery and/or SRS in the primary management of patients with brain metastasis, recently reported experiences withholding WBRT as part of primary therapy for brain metastases have not analyzed the potential effects on neurological functional status and/or neurocognition associated with the increased risk of brain tumor recurrence seen with such a strategy. We recently evaluated the risk of symptomatic brain tumor recurrence and associated neurologic deficit in 36 patients treated for newly diagnosed unresected brain metastases treated by Gamma Knife SRS alone followed by planned observation. Among the 17 patients (47%) developing brain tumor recurrence, 71% (12/17) were symptomatic and 59% (10/17) had an associated neurologic deficit. Also of interest, the author (WFR) performed a secondary analysis of a randomized phase III study of accelerated hyperfractionation (AH) versus standard accelerated fractionation (AF) in patients with unresected brain metastases. Control of brain metastases had a significant impact on MMSE. It is only among patients with 'uncontrolled" brain metastases that a drop in MMSE score is seen. Details of these studies, along with others, will be reviewed and implications with regards to the complementary role of WBRT in patients undergoing SRS for brain metastases will be discussed.

Neoadjuvant Chemotherapy Plus Conventional Radiotherapy or Accelerated Hyperfractionation in Stage III and IV Nasopharyngeal Carcinoma - A Phase II Study

A prospective phase II trial was initiated in previously untreated patients with locally advanced nasopharyngeal carcinoma (NPC). The goal was to achieve improvement in locoregional control, disease-free interval and overall survival using induction chemotherapy and to compare conventional fractionation (CF) with an accelerated hyperfractionation (AHF) regimen. Fifty patients were treated (5 AJCC Stage III, 45 Stage IV) with induction chemotherapy consisting of two cycles of cisplatin and 5-fluorouracil. Patients were then randomized between CF and AHF therapy. A clinical response to induction chemotherapy was reported in 86% of patients prior to radiotherapy (44% complete response, 42% partial response). Patients with complete or major partial responses to induction chemotherapy had a significantly better 5-year overall survival (60%) and disease-free interval (59%) than those with no response or minor partial response (15% and 18%, p = 0.009 and 0.0009). Acute radiation reactions were more pronounced in the AHF group (p = 0.0002), and the incidence of late normal tissue injury was more frequent (p = 0.08). At 5 years, the locoregional control rate was higher in the AHF arm (76%) than in the CF group (54%), but the difference was not significant (HR, 0.52; 95% CI, 0.15?2.83; p = 0.186). With a median follow-up period of 55 months (range 4?120), the 5-year disease-free interval and overall survival rates were more favorable in the AHF group than in the CF group, but the differences were not significant (59% and 54% vs. 34% and 36%, respectively, HR for disease-free interval=0.71; 95% CI, 0.27?1.88; p = 0.198 and HR for overall survival = 0.81; 95% CI, 0.37?1.78; p = 0.433). The overall treatment failure rate was 48%. Locoregional failures occurred in 12 patients (24%) and the incidence of distant metastases reached 30%. Response to induction chemotherapy is strongly predictive for locoregional control, disease-free interval and overall survival. Accelerated hyperfractionation was associated with high incidence of acute and late toxicity without significant improvement in locoregional control rate. The optimal chemotherapy dose and sequencing with radiotherapy needs to be investigated in future studies. Distant metastases remain the main cause of treatment failure in NPC.

Neurocognitive outcome in brain metastasis patients treated with accelerated fractionation (AF) vs. accelerated hyperfractionation (AH) whole brain radiotherapy (WBRT): An analysis from radiation therapy oncology group (RTOG) study 91-04

Neurocognitive outcome in brain metastasis patients treated with accelerated fractionation (AF) vs. accelerated hyperfractionation (AH) whole brain radiotherapy (WBRT): An analysis from radiation therapy oncology group (RTOG) study 91-04

A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: A report of the radiation therapy oncology group (RTOG) 9104

To compare 1-year survival and acute toxicity rates between an accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected brain metastasis. The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionation vs. standard fractionation from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastasis were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. For AH, 32 Gy in 20 fractions over 10 treatment days (1.6 Gy twice daily) was delivered to the whole brain. A boost of 22.4 Gy in 14 fractions was delivered to each lesion with a 2-cm margin. The average age in both groups was 60 years; nearly two-thirds of all patients had lung primaries. Of the 429 eligible and analyzable patients, the median survival time was 4.5 months in both arms. The 1-year survival rate was 19% in the AF arm vs. 16% in the AH arm. No difference in median or 1-year survival was observed among patients with solitary metastasis between treatment arms. Recursive partitioning analysis (RPA) classes have previously been identified and patients with a KPS of 70 or more, a controlled primary tumor, less than 65 years of age, and brain metastases only (RPA class I), had a 1-year survival of 35% in the AF arm vs. 25% in the AH arm (p = 0.95). In a multivariate model, only age, KPS, extent of metastatic disease (intracranial metastases only vs. intra- and extracranial metastases), and status of primary (controlled vs. uncontrolled) were statistically significant (at p < 0.05). Treatment assignment was not statistically significant. Overall Grade III or IV toxicity was equivalent in both arms, and one fatal toxicity at 44 days secondary to cerebral edema was seen in the AH arm. Although a previous RTOG Phase I/II report had suggested a potential benefit in patients with limited metastatic disease, a good Karnofsky performance status, or neurologic function when treated with an AH regimen, this randomized comparison could not demonstrate any improvement in survival when compared to a conventional regimen of 30 Gy in 10 fractions. Therefore, this accelerated hyperfractionated regimen to 54.4 Gy cannot be recommended for patients with intracranial metastatic disease.

Results of radiation therapy for hypopharyngeal carcinoma: impact of accelerated hyperfractionation on prognosis.

We reviewed the results of treatment in 52 patients with hypopharyngeal carcinoma who underwent radical radiation therapy using a two-fractionation scheme--conventional fractionation (CF) and accelerated hyperfractionation (AHF)--in order to evaluate the impact of the fractionation scheme on prognosis. The 5-year survival rate for the 52 patients was 19.5%, and a significantly better rate was obtained with AHF (44.4%) than with CF (12.4%). Of 27 patients who showed a complete response (CR), a higher CR rate (61%) was achieved with AHF than with CF (47%). A similar trend was also observed for T3 and T4 tumors (55% with AHF vs. 36% with CF). Multivariate analysis demonstrated that neck node status was a significant factor related to local control, and that local response and the fractionation scheme employed were significant prognostic factors for survival. The recurrence rate and recurrence within the radiation field in the AHF group was lower than in the CF group (27% vs. 50%), although the time to recurrence in the two groups did not differ greatly. Voice preservation was achieved in 20% of the patients. Considering the better survival and local control rate compared with conventional fractionation, accelerated hyperfractionation seems a preferable treatment for hypopharyngeal carcinoma.

Esophageal cancer treated with radiotherapy: Impact of total treatment time and fractionation

Purpose : Local control rate and survival rate of esophageal cancer treated with radical radiation therapy (RT) were analyzed with special respect to total treatment time and fractionation. Methods and Materials : Between 1979 and 1992, 88 patients with Stages I–III esophageal cancer were treated radically with T at Kyoto University Hospital and Wakayama Red Cross Hospital. Of the 88 patients, 52 patients were treated with conventional fractionation (1.7 – 2.0 Gy/day, five times/week), and the remaining 36 patients were treated with accelerated hyperfractionation (AHF). In 1989, we started AHF regimen for esophageal cancer. Daily fractionations were 2.0 Gy and 1.2 Gy (field-in-field), or 1.5 Gy and 1.5 Gy at 5- to 6-h interval. Most of the patients treated with AHF received the total radiation dose of 64–68 Gy. Twenty-seven patients were treated with intraluminal brachytherapy (IBT) as boost therapy following external RT. Fourteen patients were treated with IBT following AHF. Results : The median of treatment time of AHF was approximately 2 weeks shorter than that of conventional fractionation. Local control rate at 1 year were 47% for AHF, which was significantly higher than that for conventional fractionation (22%, p < 0.05). The improvement of local control by AHF was responsible for a trend to an improved cause-specific survival ( p = 0.07). Local control rates at 1 year were plotted as a function of total treatment time. The slope of the linear regression line was −2.3 ± 0.5% per day ( p < 0.025) for patients treated with external RT alone, indicating a 2.3% per day loss in local control. Pretreatment and treatment parameters were evaluated in a multivariate analysis for the end point of local control. T stage (T1, 2 vs. T3, 4; p = 0.003) and fractionation schedule ( p = 0.03) were independent of prognostic significance. Patients could tolerate the AHF well, although esophageal stenosis was noted frequently as a late toxicity. Conclusion : Accelerated hyperfractionation was the most important treatment-related variable in this patient population. Total treatment time may have a significant impact on the treatment outcome for esophageal cancer.

Accelerated versus conventional fractionation in the postoperative irradiation of locally advanced head and neck cancer: influence of tumour proliferation

Fifty-six patients with locally advanced head and neck squamous cell carcinoma were subjected to adjuvant radiotherapy after radical surgery with randomisation to either conventional fractionation (CF), comprising 50 Gy/25 F/5 weeks, or to accelerated hyperfractionation (AHF) to a dose of 42 Gy/30 F/11 days (3 F/day), a dose/F of 1.4 Gy and an interfraction interval of 4 h. The in vitro [ 3H]thymidine labelling index (TLI) was determined as an indicator of tumour proliferation. Early mucosal reactions were somewhat more severe after AHF than after CF and the peak was attained earlier. The actuarial 3-year complication rate was significantly lower in the AHF (64%) than in the CF group (87%). This is probably related to a smaller fraction size and a lower total dose. The overall 3-year disease-free survival amounted to 46 ± 7%. Sex, the anatomical site, the nodal status, the performance status and TLI have been shown to be significant prognostic factors, but only the latter two proved to be independent covariates. Overall, the type of fractionation did not seem to influence survival. However, AHF seemed to offer higher survival probabilities in fast growing tumours and this attained a significant level for tumours with TLI >; 10.4% ( T pot < 4.5 days). However, CF and AHF were associated with similar survival rates in slowly growing tumours. The relative effectiveness of the CF and AHF schedules is predictable on the basis of the linear-quadratic system. In the case of tumour response, a time factor has to be included assuming that accelerated repopulation of microscopic residues occurs from the outset. A correction for incomplete repair has to be applied in case of short interfraction intervals.