Patterns of failure in patients with locally advanced head and neck cancer treated postoperatively with irradiation or concomitant irradiation with Mitomycin C and Bleomycin

PURPOSE: The long term results and patterns of failure in patients with squamous cell head and neck carcinoma (SCHNC) treated in a prospective randomized trial in which concomitant postoperative radiochemotherapy with Mitomycin C and Bleomycin (CRT) was compared with radiotherapy only (RT), were analyzed. PATIENTS AND METHODS: Between March 1997 and December 2001, 114 eligible patients with Stage III or IV SCHNC were randomized. Primary surgical treatment was performed with curative intent in all patients. Patients in both groups were postoperatively irradiated to the total dose of 56-70 Gy. Chemotherapy included Mitomycin C 15 mg/m2 after 10 Gy and 5 mg of Bleomycin twice weekly during irradiation. Median follow-up was 76 months (48-103 months). RESULTS: At 5 years in the RT and CRT arms, the locoregional control was 65% and 88% (p = 0.026), disease-free survival 33% and 53% (p = 0.035), and overall survival 37% and 55% (p = 0.091) respectively. Patients who benefited from chemotherapy were those with high-risk factors. The probability of distant metastases was 22% in RT and 20% in CRT arm (p = 0.913), of grade III or higher late toxicity 19% in RT and 26% in CRT arm (p = 0.52) and of thyroid dysfunction 36% in RT and 56% in CRT arm (p = 0.24). The probability to develop a second primary malignancy (SPM) was 34% in the RT and 8% in the CRT arm (p = 0.023). One third of deaths were due to infection, but there was no difference between the 2 groups. CONCLUSION: With concomitant radiochemotherapy, locoregional control and disease free survival were significantly improved. Second primary malignancies in the CRT arm compared to RT arm were significantly less frequent. The high probability of post treatment hypothyroidism in both arms warrants regular laboratory evaluation.     

Sensori-neural hearing loss in patients treated with irradiation for nasopharyngeal carcinoma

The present investigation has been carried out to evaluate the sensitivity of the inner ear to irradiation. Cochlear function was tested in a cohort of 22 patients before and 7-84 months after receiving external irradiation for nasopharyngeal carcinoma. The pre-irradiation sensori-neural hearing threshold at 500, 1000, 2000, and 4000 Hz was used as a baseline for the individual patient, and the observed sensori-neural hearing loss (SNHL) was calculated as the difference between pre- and post-irradiation values. The pre-irradiation hearing level or patient age was not correlated with the actual SNHL. In contrast, there was a significant correlation between the total radiation dose to the inner ear and the observed hearing impairment. SNHL was most pronounced in the high frequencies, with values up to 35 dB (4000 Hz) and 25 dB (2000 Hz) in some patients. The latent period for the complication appeared to be 12 months or more. The deleterious effect of irradiation on the hearing should be kept in mind both in treatment planning and in the follow-up after radiotherapy.     

Patterns of recurrence in bladder cancer treated by irradiation and/or cystectomy

Between 1949 and 1971, 451 patients with bladder cancer were treated by radiation therapy and/or radical cystectomy at the Memorial Sloan-Kettering Cancer Center. Radical cystectomy alone was the treatment for 137 patients in Group 1. In Group 2, 109 patients received radiation therapy to an average tumor dose of 6000 rad in 6 weeks ± 1 year before radical cystectomy for persistent, recurrent or new lesions. Planned preoperative irradiation consisted of either 4000 rad in 4 weeks for 119 patients in Group 3, or 2000 rad in 1 week for 86 patients in Group 4, ± 6 weeks and 2 days, respectively, before radical cystectomy.The determinate over-all distant and/or local recurrence rate was 49% for Group 1 and 37–45% for Groups 2–4. Local recurrence alone occurred in 28% of Group 1 patients and 14–16% of those in Groups 2–4. Distant metastases developed in 21% of Group 1 patients and 22–28% of Group 2–4 patients. A reduced incidence of pelvic recurrence was associated with radiation-induced stage reduction for Group 2–4 clinically high and low stage tumors, especially when the histologic grade was high. Similar frequencies of extrapelvic metastases in the four groups were maintained in clinically low and high stage tumors of low or high histological grade.     

鼻咽癌放射治疗失败原因分析

目的：研究鼻咽癌放射治疗失败原因,为制定鼻咽癌治疗策略提供依据。方法：１９９２年８月至１９９３年１２月,６２１例鼻咽癌患者Ｉ～Ⅳ期分别为５．５％,２５．０％,４７．８％及２１．７％,治疗前均行ＣＴ或ＭＲ检查,经鼻咽病理证实的非转移鼻咽癌接受根治术放射治疗。鼻咽腔内残留病灶,给予腔内后装治疗。随诊方法根据症状、体征、病理学及相关部位的影像学检查,生存分析用Ｋａｐｌａｎ－Ｍｅｉｅｒ法,生存指标采用总生     

Patterns of locoregional failure in women with early-stage breast cancer treated by whole breast irradiation in the lateral isocentric decubitus position: Large-scale single-centre experience

PurposeThe purpose of this study was to evaluate locoregional control and describe the patterns of failure in patients with breast cancer receiving whole breast radiotherapy in the isocentric lateral decubitus position technique.Patients and methodsIn a series of 832 consecutive female patients with early-stage breast cancer including invasive and in situ tumours treated by breast-conserving surgery followed by three-dimensional conformal whole breast irradiation in the isocentric lateral decubitus position between 2005 and 2010, all patients who experienced locoregional recurrence were studied. Five-year recurrence-free and overall survival rates were calculated. Regional recurrence mapping patterns were also determined.ResultsThe median age of this series of 832 women was 61.5 years (range: 29–90 years). Various types of fractionation were used: 50 Gy in 25 fractions (17.9%), 66 Gy in 33 fractions (50 Gy in 25 fractions to breast followed by sequential boost to tumour bed to a total dose 66 Gy in 33 fractions.) (46.5%), 40 Gy in 15 fractions or 41.6 Gy in 13 fractions (26.1%) and 30 Gy in 5 fractions (9.5%). With a median follow-up of 6.4 years, only 36 patients experienced locoregional recurrence and no association with the fractionation regimen was identified (P = 0.2). In this population of 36 patients, 28 (3.3%) had “in-breast” local recurrences (77.8%), two had local recurrences and regional lymph node recurrence (5.6%), and six had regional lymph node recurrence only (in non-irradiated areas; 16.6%). The median time to recurrence was 50 months. Complete mapping of patterns of recurrences was performed and, in most cases, local recurrences were situated adjacent to the primary tumour bed. Cases of local recurrences presented a significantly lower distant metastasis rate (P < 0.001) and had a significantly longer overall survival compared to patients with regional lymph node recurrence (P < 0.001). However, multivariate Cox regression analysis showed that the site of recurrence had no significant impact on overall survival (P = 0.14).ConclusionThe results of this study indicate a low local recurrence rate. Further careful follow-up and recording of recurrences is needed to improve the understanding of patterns of recurrence.     

Patterns of failure following radiation with and without chemotherapy in patients with nasopharyngeal carcinoma

PURPOSE: Aim of this study was to retrospectively evaluate patterns of failure, results, and prognostic factors for patients with nasopharyngeal cancer (NPC) following radiotherapy (RT) with and without concurrent chemotherapy (RCT). PATIENTS AND METHODS: Between 1978 and 1999, a total of 101 patients with NPC were treated in our hospital, of whom 53 received external megavoltage RT alone with a median total dose of 76 Gy (1978-1988), and 48 patients had RCT (1989-1999). For RCT a combination of 5-FU and cisplatin was used together with a median total dose of 72 Gy. Patterns of relapse, survival rates and toxicity as well as prognostic factors were evaluated retrospectively. RESULTS: RCT was associated with a marked reduction in distant metastases: 6/48 (13%) vs. 17/53 (32%) after RT alone. Locoregional tumor persistence was only marginally lower with RCT: 10/48 (21%) vs. 17/53 (32%) following RT. Patients with RCT demonstrated a survival advantage compared to those with RT alone (5-year overall survival (OS): 64% vs. 44%, p = 0.1). OS, disease-specific survival and locoregional control rates were 53, 57, and 78% at 5 years and 47, 51 and 78% at 10 years, respectively. OS was significantly affected by histology (p = 0.007), the patients' age (p = 0.009) and gender (p = 0.01). CONCLUSION: This retrospective study provides further evidence that both reduction of distant metastasis and enhanced local tumor control by combined radiochemotherapy may be associated with improved survival rates in NPC compared to radiation alone. Concurrent RCT is therefore considered the preferable treatment option, however, confirmation in randomized trials is still warranted.     

Patterns of locoregional failure in stage III non-small cell lung cancer treated with definitive chemoradiation therapy

PurposeChemoradiation therapy (CRT) is the core treatment of locally advanced non-small cell lung cancer (LA-NSCLC), but potential toxicities limit radiation therapy dose. These toxicities, plus the advent of increasingly conformal radiation therapy, have prioritized target definition and the use of involved-field radiation therapy (IFRT). Published data largely focus on regional rather than local failure patterns. We report our pattern-of-failure experience treating patients with LA-NSCLC with definitive CRT, focusing on both local and regional recurrences with detailed dosimetric analyses of failure location.Methods and materialsPatients treated between December 2004-2010 were included. Imaging scans from date of failure were fused with the RT-planning CT scan, and recurrent nodes were contoured to determine if the recurrence was in a previously irradiated region, defined as involved nodal recurrence (INR) versus elective nodal recurrence (ENR). Local failures were contoured and identified as in-field, marginal, or out-of-field based on dose received. Actuarial overall survival (OS) and progression-free survival (PFS) were calculated, and the cumulative incidences of local, regional, locoregional, and distant recurrence (CILR, CIRR, CILRR, CIDR) were determined with death as a competing risk.ResultsOne hundred five patients were included with a median survival of 21.8 months. The 3-year OS and PFS were 36% and 22%, respectively. The 3 year CILRR, CILR, CIRR, CIDR were 41%, 38%, 40%, and 58%, respectively. Thirty patients failed regionally, but only 7 patients developed an ENR with no concurrent local failure or INR, and only 1 of these patients did not develop distant metastases within 1 month of recurrence. A total of 21 patients (20%) developed an ENR with or without other areas of recurrence.ConclusionsElective regional recurrences rarely occurred as the sole site of failure, despite the use of IFRT. Moreover, the pattern of local failure was entirely in-field. These data strongly support field design focusing on gross nodal and primary disease.     

Recurrent locally advanced nasopharyngeal carcinoma treated with heavy charged particle irradiation.

Between June 1981 and May 1990, 11 patients with recurrent locally advanced nasopharyngeal carcinoma were treated with heavy charged particle radiation at Lawrence Berkeley Laboratory. All patients had previously undergone full course radiotherapy to a median dose of 70.2 Gy [range 61-81 Gy]. Median time to recurrence was 18.2 months. At the time of heavy charged particle radiotherapy treatment, all had evidence of invasion of the base of skull and 7 of 11 had cranial nerve deficits. None of the patients were candidates for brachytherapy because of tumor extent or poor geometry. The tumor histology was squamous cell carcinoma in 10 patients and lymphoepithelioma in one patient. Ten of the 11 patients had received chemotherapy prior to re-irradiation. The heavy charged particle tumor dose delivered ranged from 31.80 GyE to 62.30 GyE (average 50.25 GyE, median 50 GyE). Local control was achieved in 45%. Median survival was 42 months. Actuarial survival was 59% at 3 years and 31% at 5 years (Kaplan-Meier). There were no fatal complications. The results in treating locally advanced recurrent nasopharyngeal carcinoma with heavy charged particles appear superior to those reported by others using photon therapy.     

Patterns of nasopharyngeal cancer mortality in the United States

We examined the geographic pattern of nasopharyngeal cancer (NP cancer) mortality in the United States using economic sub-regions (ESRs) as the basis for analysis. The distribution of 15,145 deaths from NP cancer over the years 1950-1979 revealed clustering in the 119 ESRs that was not detected in analyses of distribution by the 48 states, 506 state economic areas or 3,056 counties or combinations of counties of the coterminous United States. NP cancer mortality among white males was concentrated on the south-east Atlantic and Gulf coasts. This newly described pattern is not due to any recent changes in mortality rates and should provide leads to further epidemiologic study.     

Patterns of failure and survival in locally advanced carcinoma of the uterine cervix treated with high dose-rate intracavitary irradiation system.

We retrospectively analyzed 71 patients with locally advanced carcinoma of the uterine cervix treated by irradiation using high dose-rate intracavitary brachytherapy between 1978 and 1985. Seven patients were Stage IIIa, 46 Stage IIIb, and 18 Stage IVa. Five-year survivals for Stage IIIa, IIIb, and IVa were 71.4, 60.9, and 16.7%, respectively. An analysis of patterns of failure demonstrated that loco-regional recurrences were observed in 1 (14.3%) for Stage IIIa, 6 (13.0%) for Stage IIIb, and 9 (50.0%) for Stage IVa. The incidence of recurrence outside the pelvis observed in Stage IIIb patients (7 para-aortic nodes, 5 distant metastases) was much higher than that of local recurrence. Five patients (7.0% of the total: 1 with Stage IIIa, 3 with Stage IIIb, 1 with Stage IVa) required surgery to manage the complications. These data suggest that a high dose-rate intracavitary irradiation system is an effective tool for the treatment of cervical cancer. Further efforts to control metastatic lesions outside the pelvis are required for patients with Stage IIIb. To increase a loco-regional control rate for patients with Stage IVa disease, it is important to give additional treatment such as chemotherapy in conjunction with radiation therapy.     

鼻咽癌IMRT后局部与区域失败模式研究

目的 分析鼻咽癌患者IMRT后局部与区域失败的剂量学模式,为进一步提高鼻咽癌疗效提供临床依据。方法 分析2007—2012年我院收治的364例初治无远处转移鼻咽癌患者的局部与区域失败模式,失败模式定义为V_95%(95%等剂量曲线包括的复发灶体积)≥95%定义为野内复发,20%≤V_95%<95%为野边缘复发,V_95%<20%为野外复发。生存率计算采用Kaplan-Meier法。     

Patterns of regional failure in stage III non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and resection

PurposeTreatment of locally advanced non-small cell lung cancer (LA-NSCLC) involves definitive chemoradiation therapy (CRT) or neoadjuvant CRT and resection, but radiation treatment volumes remain in question. With CRT, involved-field radiation therapy (IFRT) is replacing elective nodal irradiation, reducing toxicity, and allowing dose escalation. However, prior reports of IFRT describe failures only after radical CRT; with improved local control after resection, IFRT may lead to more regional recurrences. Our objective is to evaluate pattern-of-failure in patients with LA-NSCLC treated with split-course IFRT, chemotherapy, and subsequent surgery.Methods and MaterialsPatients treated between December 2004 and 2010 were included. Imaging scans demonstrating failure were fused into the radiation therapy planning computed tomography, and recurrent nodes were contoured to determine pattern-of-failure (involved versus elective nodal failure [INF vs ENF]). Locoregional progression-free survival and distant metastasis-free survival were calculated using Kaplan-Meier methodology. The cumulative incidence of regional recurrence (CIRR) was determined with death as a competing risk.ResultsForty-five patients met inclusion criteria, and patients with RR had a lower rate of pN0 than those without RR (20% vs 60%, P = .02). With a median follow-up of 2.9 years, median survival was not reached, and 3-year locoregional progression-free survival and distant metastasis-free survival were 53% and 35%, respectively. Two and 3-year CIRR were 25% and 33%, respectively. There were no local failures. Thirteen (29%) patients had RR, 8 with INF only and 5 with ENF alone or both, totaling 27 recurrences. Only 2 (4%) ENF occurred without INF, both with distant metastasis, and no elective node was the first and only site of failure.ConclusionsOur data suggest that IFRT does not compromise regional control in the neoadjuvant management of LA-NSCLC. Tailoring nodal volumes may improve treatment-related morbidity and allow for dose intensification of involved nodes. Further research is necessary to improve regional and distant control.     

Axillary lymph node failure in patients treated with accelerated partial breast irradiation

BACKGROUND:

Data on the risk of axillary failure (AF) after accelerated partial breast irradiation (APBI) are limited. In this study, the authors determined the rate of AF and regional lymph node failure (RNF) in patients who received various forms of APBI and identified factors that were associated with its occurrence.

METHODS:

In total, 534 patients with early stage breast cancer were treated at William Beaumont Hospital with APBI, including 466 patients (87%) with invasive breast cancer and 68 patients (13%) with ductal carcinoma in situ. Clinical variables (patient age, tumor location), pathologic variables (tumor size, grade, estrogen receptor status, margin status, lymph node status), and treatment‐related variables (receipt of hormone and systemic chemotherapy) were analyzed to determine which factors were associated with AF and RNF. The median length of follow‐up was 63 months (range, 1‐201 months).

RESULTS:

The 5‐year actuarial AF rate was 0.19%. Three patients (0.56%) developed RNF (all patients initially had invasive breast cancer) with a 5‐year actuarial rate of 0.37%. Two of the regional recurrences were in the supraclavicular fossa, and 1 was in the axilla. No variables were associated with AF. However, patient numbers were very small. The median survival after RNF was 0.8 years (range, 0.3‐1.7 years), and 2 of the 3 patients died of disease.

CONCLUSIONS:

The rate of AF and RNF after APBI was low and appeared to be similar to the rate observed with whole‐breast irradiation. No variables were associated with a higher rate of AF after APBI. Cancer 2012;. © 2011 American Cancer Society.     

Prognostic factors in limited rectal cancer treated with intracavitary irradiation

At the Centre Georges-Fran?ois Leclerc of Dijon, 91 limited rectal tumors received a complete intracavitary 50 kV contact radiotherapy alone or associated with interstitial brachytherapy according to the guidelines of J. Papillon. Nineteen had a villous adenoma and 72 a well or moderately differentiated rectal adenocarcinoma. The majority of patients had contra-indications for major surgical procedures. The median age was 70 years. Seventy-six percent (69/91) of the rectal tumors remained free from local recurrence. After salvage therapy, the local control was 91% (83/91). Sphincter preservation was obtained in 85% (77/91). "De novo" adenocarcinomas developed on pre-existing benign pathology and villous adenomas were not significantly different with regard to local control (76% resp. 75% versus 59.5%; p = 0.22). According to the Dijon clinical staging system, the local relapse-free survival at 5 years was 97% for CS T1A, 77% for CS T1B, 65% for CS T2A, and 60% for CS T2B. Tumors of the anterior rectal wall had a better local control rate than lateral and posterior primaries (100% versus 63% versus 67%). For the middle rectum, the local relapse-free survival was 94% compared to 54% of the upper and 77% of the lower rectum. Four additional patients had a preoperative intracavitary therapy and salvage surgery for incomplete tumor regression; the complete remission rate is 96% (91/95). Intracavitary radiotherapy alone is an effective treatment for limited rectal cancers. Contact X ray therapy can be used alone in CS T1A whereas a combination of contact X ray therapy and interstitial brachytherapy is often the optimal approach in CS T1B and CS T2A. In CS T2B, our data do not support the use of intracavitary techniques alone. In these cases, the sequence external irradiation followed by an interstitial implant seems of interest and deserves further evaluation with more patients and follow-up.     

Patterns of failure in a randomized trial of adjuvant chemotherapy in postmenopausal patients with early breast cancer treated with tamoxifen.

BACKGROUND: We studied the effect of adjuvant anthracycline-based chemotherapy in postmenopausal patients with resected early breast cancer treated with adjuvant tamoxifen. PATIENTS AND METHODS: The trial included 835 patients with either axillary lymph node involvement, or tumors with histological grade II or III. They were randomized after local surgery to receive either tamoxifen (TAM group) or tamoxifen plus chemotherapy (TAM-CT group) consisting of six courses of 5-fluorouracil, doxorubicin and cyclophosphamide (FAC), or 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC). Radiotherapy was given after completion of adjuvant chemotherapy in the TAM-CT group and after surgery in the TAM group. RESULTS: The 5-year disease-free survival (DFS) rates were 73% in the TAM group and 79% in the TAM-CT group (log-rank test, P = 0.06). The 5-year overall survival rates were 82% and 87%, respectively (P = 0.06). The 5-year distant metastasis rates were 22% and 16% (P = 0.02), and the 5-year local recurrence rates were 6% and 4%, respectively (P = 0.23). There were no significant differences for contralateral breast cancer or other new primary malignancies. Chemotherapy tended to be more effective for patients who had tumors without estrogen receptors (trend test, P = 0.05). CONCLUSIONS: Anthracycline-based chemotherapy administered to postmenopausal patients receiving adjuvant tamoxifen gave a borderline significant benefit on overall and DFS, mainly by a reduction in distant metastases. Delaying radiotherapy after six courses of chemotherapy did not affect local control after up to 10 years of follow-up.     

Patterns of failure in children with medulloblastoma treated with 3D conformal radiotherapy.

BACKGROUND AND PURPOSE: Craniospinal irradiation for medulloblastoma is one of the most complex techniques employed in radiotherapy. Many reports stress the impact of irradiation quality on survival in these patients. Our report presents the outcome and patterns of failure for 95 patients treated with 3D conformal radiotherapy (3D-CRT). MATERIALS AND METHODS: From 1998 to 2003, 95 children with medulloblastoma received 3D conformal radiotherapy. All of them were previously treated with surgery and chemotherapy. The brain and upper spinal cord were treated with two lateral 6MV photon fields. In four patients, the cribriform plate was irradiated by the additional field. For primary tumour bed we applied two or three photon beams. Spinal cord was irradiated either with 18-20MeV electron fields or with a mixed beam. RESULTS: With a median follow-up of 48 months, 32/95 patients suffered a multifocal (21) or isolated (11) recurrence. We evaluated every primary site of failure. In all patients, the recurrence appeared within the isodose level of 95-100%. CONCLUSIONS: Patterns of failure in medulloblastoma patients treated with 3D conformal radiotherapy indicated that the relapse was mainly associated with poor response to pre-irradiation chemotherapy. We believe that 3D conformal radiotherapy allows avoiding failures, related to radiotherapy uncertainties.     

N0期鼻咽癌颈部未达诊断标准的肿大淋巴结接受不同照射剂量的疗效比较

目的探讨N0期鼻咽癌颈部未达诊断标准的肿大淋巴结区最佳的照射剂量。方法回顾性分析358例中上颈部存在未达阳性淋巴结诊断标准的N0期鼻咽癌的临床资料,192例的可疑淋巴结区接受52 Gy照射(A组),166例的此区域接受60～64 Gy照射(B组)。采用Kaplan-Meier计算总生存率、无颈部复发生存率和无远处转移生存率,Logrank进行差异检验。结果 T1及T2期,两组的生存率差异无统计学意义,而T3及T4期,B组生存率明显高于A组。B组的T2、T3、T4期的无颈部区域复发生存率明显高于A组,但T1期无明显差异。B组的T3及T4期的无远处转移生存率明显高于A组,而T1及T2期无明显差异。结论 T2、T3、T4N0期患者,若中上颈部存在未达诊断标准的肿大淋巴结,应给予至少60 Gy的照射剂量。     

鼻咽癌放射治疗的失败模式

目的分析鼻咽癌患者治疗失败模式及其与治疗前相关因素的关系,探求更好的治疗方案。方法自1990年1月1日至1999年5月30日收治首程治疗的患者905例。分析放射治疗后失败的模式及其影响因素。组间差别用χ2检验。结果254例首次治疗后出现失败,失败率为28.1%。5、10年局部控制率分别为81.7%、76.7%。首次治疗失败中局部失败104例,占失败患者的40.9%;远地转移124例,占失败患者的48.8%。79.5%的局部失败和88.6%远地转移出现在治疗后3年内。骨转移是最常见的部位,其次是肝和肺。1992年福州T、N分期和临床分期对局部失败的影响无显著性差异(P>0.05),对远地转移的影响有极显著性差异(P<0.01)。结论远地转移已成为鼻咽癌放射治疗失败的主要原因之一,如何降低T4、N3期患者的远地转移是当前面临的课题。     

Repeat megavoltage irradiation of pituitary and suprasellar tumors

From 1965 to 1984, ten patients with suprasellar or pituitary tumors received repeat courses of radiation therapy at the Joint Radiation Oncology Center of the University of Pittsburgh. The radiation doses varied between 36.00 to 53.65 Gy for the first treatment course and from 35.00 to 49.60 Gy for retreatment. Six patients were treated for pituitary tumors, two for germinoma, one for optic glioma, and one for craniopharyngioma. One died of disease progression 19 years after a second course of radiation. Two patients were dead of intercurrent disease 0.2 and 1.5 years after repeat radiation. The remainder are free of disease progression 1.6 to 20.5 years after repeat irradiation. Optic neuropathy developed in one patient 1.3 years following a second course of treatment to 40 Gy in 20 fractions administered 7.5 years after initial treatment to 46 Gy in 23 fractions. Neither the Nominal Standard Dose nor the Neuret formula provided an adequate estimate of the repair of radiation. An estimation that 40% of the original radiation dose effect is still present appears to be a reasonable "rule of thumb" guideline to account for prior radiotherapy.