Mechanical strength vs. degradation of a biologically-derived surgical mesh over time in a rodent full thickness abdominal wall defect.

The use of synthetic surgical mesh materials has been shown to decrease the incidence of hernia recurrence, but can be associated with undesirable effects such as infection, chronic discomfort, and adhesion to viscera. Surgical meshes composed of extracellular matrix (i.e., biologically-derived mesh) are an alternative to synthetic meshes and can reduce some of these undesirable effects but are less frequently used due to greater cost and perceived inadequate strength as the mesh material degrades and is replaced by host tissue. The present study assessed the temporal association between mechanical properties and degradation of biologic mesh composed of urinary bladder matrix (UBM) in a rodent model of full thickness abdominal wall defect. Mesh degradation was evaluated for non-chemically crosslinked scaffolds with the use of (14)C-radiolabeled UBM. UBM biologic mesh was 50% degraded by 26 days and was completely degraded by 90 days. The mechanical properties of the UBM biologic mesh showed a rapid initial decrease in strength and modulus that was not proportionately associated with its degradation as measured by (14)C. The loss of strength and modulus was followed by a gradual increase in these values that was associated with the deposition of new, host derived connective tissue. The strength and modulus values were comparable to or greater than those of the native abdominal wall at all time points.

Lung density as measured by computerized tomography: implications for radiotherapy.

Accurate dose calculations for radiotherapy planning require a detailed knowledge of the internal anatomy of the patient both in terms of geometry and density. Computed tomography (CT) is presently the best means of providing these data. Fifty-eight patients who had scans of the thorax for radiotherapy planning were studied. The CT numbers were converted to relative electron densities and average lung densities were obtained for every patient. A linear correlation of lung density with age was found with the mean lung density of 0.35 at an age 5 years and 0.19 at an age of 80. The effect of scanning the patient under full inspiration, full expiration or normal shallow breathing conditions was analyzed. At the age of 5 years the expiration and inspiration average lung densities were 0.36 and 0.20, while at the age of 80 years they were 0.22 and 0.16, respectively. Respiratory volume changes were linearly correlated with changes in relative electron density. Differences in lung density between expiration and inspiration scans were found to demonstrate a similar trend with age as the relationship between vital capacity and age. The dosimetric and the possible clinical implications of lung density measurements for radiotherapy are considered. In particular, dose calculations were performed using scans taken under a number of different respiratory conditions. Doses calculated for a single cobalt-60 beam can differ by more than 25% when comparing a full inspiration scan to a normal breathing scan. A similar comparison for a parallel pair distribution on the lung yields a difference of about 3% while a typical three field technique for treating cancer of the esophagus shows a difference of nearly 10%.

Epidermoid anal cancer: treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C.

One hundred ninety-two patients with primary epidermoid cancer of the anal canal were treated by a series of prospectively designed, sequential non-randomized protocols of radiation alone (RT), radiation with concurrent 5-Fluorouracil and Mitomycin C (FUMIR), or radiation with concurrent 5-Fluorouracil only (FUR). The 5-year cause-specific survival rates were 69% overall, 68% RT, 76% FUMIR, 64% FUR. The primary tumor was controlled by radiation with or without chemotherapy in 68% (130/191) overall, 56% (32/57) by RT, 86% (59/69) by FUMIR, 60% (39/65) by FUR. The results with FUMIR were significantly better than with either RT alone or FUR, and except in tumors up to 2 cm in size, this superiority was found in all T stages. Regional lymph node metastases were controlled in 33 of 38 (87%) overall. The finding of clinically detectable regional lymph node metastases at presentation did not affect survival significantly in any treatment group. Anorectal function was preserved in 88% of the patients in whom the primary tumor was controlled, and in 64% overall. The delivery of 5FU and MMC concurrently with uninterrupted radical irradiation, 50 Gy in 20 fractions in 4 weeks, produced severe acute and late normal tissue morbidity. Split course treatment, and reduction of the daily fractional dose to 2 Gy, diminished the severity of normal tissue damage. Omission of Mitomycin C reduced acute hematological toxicity, but was associated with a decreased primary tumor control rate. The most effective treatment protocols as measured by survival rates, primary anal tumor control rates, and the likelihood of conservation of anorectal function included the administration of both Mitomycin C and 5-Fluorouracil concurrently with radiation therapy.

Quantitative effect of combined chemotherapy and fractionated radiotherapy on the incidence of radiation-induced lung damage: a prospective clinical study.

PURPOSE: The objective of this work was to assess the incidence of radiological changes compatible with radiation-induced lung damage as determined by computed tomography (CT), and subsequently calculate the dose effect factors (DEF) for specified chemotherapeutic regimens. METHODS AND MATERIALS: A prospective, clinical study was conducted to determine the response of normal lung tissue to combined chemotherapy and radiotherapy. Radiation treatments were administered once daily, 5 days-per-week. Six clinical protocols were evaluated: ABVD (adriamycin, bleomycin, vincristine, and DTIC) followed by 35 Gy in 20 fractions; MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) followed by 35 Gy in 20; MOPP/ABVD followed by 35 Gy in 20; CAV (cyclophosphamide, adriamycin, and vincristine) followed by 25 Gy in 10; and 5-FU (5-fluorouracil) concurrent with either 50-52 Gy in 20-21 or 30-36 Gy in 10-15 fractions. CT examinations were taken before and at predetermined intervals following radiotherapy. CT evidence for the development of radiation-induced damage was defined as an increase in lung density within the irradiated volume. The radiation dose to lung was calculated using a CT-based algorithm to account for tissue inhomogeneities. Different fractionation schedules were converted using two isoeffect models, the estimated single dose (ED) and the normalized total dose (NTD). RESULTS: A total of 102 patients were entered and 70 completed the study. Forty-two patients developed CT changes compatible with lung damage. The actuarial incidence of radiological pneumonitis was 71% for the ABVD, 49% for MOPP, 52% for MOPP/ABVD, 67% for CAV, 73% for 5-FU radical, and 58% for 5-FU palliative protocols. Depending on the isoeffect model selected and the method of analysis, the DEF was 1.11-1.14 for the ABVD, 0.96-0.97 for the MOPP, 0.96-1.02 for the MOPP/ABVD, 1.03-1.10 for the CAV, 0.74-0.79 for the 5-FU radical, and 0.94 for the 5-FU palliative protocols. CONCLUSION: Quantitative dose effect factors (DEF) were measured by comparing the incidences of CT-observed lung damage in patients receiving chemotherapy and radiotherapy to those receiving radiotherapy alone. The addition of ABVD or CAV appeared to reduce the tolerance of lung to radiation.

Combined radiation therapy, mitomycin C, and 5-fluorouracil for locally recurrent rectal carcinoma: results of a pilot study.

Twenty-two patients underwent combined radiation therapy (XRT), mitomycin C (MMC), and 5-fluorouracil (5FU) for rectal carcinoma, locally recurrent following either abdominoperineal or anterior resections. All patients presented with symptomatic unresectable pelvic cancer. The protocol XRT doses were 45-50 Gy/20/4-6 weeks. Chemotherapy consisted of MMC 10 mg/m2 on day 1, and 5FU 15 mg/kg/day on days 1, 2, and 3 of XRT, both given by intravenous bolus injection. Only 2 of 22 patients remained NED at 5 years following treatment. All but four patients eventually experienced progression of pelvic disease. Ten of 22 patients were unable to complete the treatment protocol because of excessive acute hematological and gastrointestinal toxicity. Five patients developed neutropenic sepsis, one of whom died. Combined XRT, MMC, and 5FU as used in this study had no apparent advantage over XRT alone in terms of pelvic disease or survival, and produced significant toxicity.

Postoperative local abdominal irradiation for cancer of the colon above the peritoneal reflection.

A retrospective analysis of 82 patients with cancer of the colon above the peritoneal reflection who received postoperative local abdominal irradiation was undertaken to assess the survival, patterns of failure, and toxicity of treatment. Forty-eight patients (adjuvant group) had a complete resection, but were felt to be at high risk for local relapse and received postoperative local abdominal irradiation. Thirty-four patients had gross residual disease following surgery. The 5-year actuarial survival and local relapse free survival were 67 and 67%, respectively, in the adjuvant group. In this group, local relapse was observed in 9 of 28 patients with Stage C disease in contrast to 3 of 20 patients with Stage B2 disease; 1 of 14 patients with lesions in the right colon failed locally compared to 11 of 35 patients with lesions in the left. Only 2 of the 34 patients with gross residual disease remained relapse free from 93% of patients having a component of local failure. The majority of the treatment morbidity was seen in patients with gross residual disease. Prospective randomized studies should be done to determine the efficacy of postoperative irradiation in patients with colon carcinoma who are at high risk for local recurrence following surgical resection.

Carcinoma of the tonsil: the effect of dose-time-volume factors on local control.

Between 1970 and 1979, 372 patients with squamous cell carcinoma of the tonsil were treated with primary irradiation therapy, with salvage surgery for failures. The median age was 60 years and the male to female ratio was 2:1. The staging system used was the 1974 UICC TNM system. There were 47 T1 lesions (13%), 161 T2 lesions (43%), and 164 T3 lesions (44%). Regional nodes were not palpable in 173 (46%); 122 had N1 nodes (33%), 6 had N2 nodes (2%) and 71 had N3 nodes (19%). All patients received external beam radiation which was supplemented in 68 patients with a radioactive implant for disease into adjacent tongue. The overall survival for all patients was 38% at 5 years and 54% when corrected for intercurrent disease. Local control was 87% for T1 lesions, 68% for T2 lesions and 50% for T3 lesions. Regional control was 96% for N0, 67% for N1 and 37% for N2-3. A detailed dose-time-volume analysis revealed that increasing volume improved local control in T1 and T2 lesions (77% had local control if the volume was greater than 80 cm2 versus 53% if the volume was less than 80 cm2, p = 0.014), except for T3 lesions. Increasing the dose in the range of 5000 to 6500 rad had no significant effect on primary control in any stage of disease. The addition of a radioactive implant did not increase local control if disease extended into the tongue (57% local control if implant, 52% if no implant). This study demonstrates the significance of adequate treatment volume in local control for carcinoma of the tonsil. No significant dose response was found and subsequent surgery was not compromised when a moderate dose of radiation was used.

A randomized trial of radiation therapy compared to split course radiation therapy combined with mitomycin C and 5 fluorouracil as initial treatment for advanced laryngeal and hypopharyngeal squamous carcinoma.

Two hundred and twelve patients with previously untreated advanced squamous carcinoma of the larynx or hypopharynx were randomized to receive initial treatment with radiotherapy, 50 Gy in 20 fractions in 28 days or split course radiotherapy and concurrent chemotherapy, 25 Gy in 10 fractions in 14 days followed by a 4 week rest and a further 25 Gy in 10 fractions in 14 days starting on day 43; Mitomycin C was given on day 1 and day 43 and 5FU continuous infusions on days 1--4 and days 43--46. Surgery was reserved for persistent or recurrent disease. Two hundred and nine of the 212 patients randomized were included in the analyses. Outcome analyses were performed at a median follow-up interval of 4.4 years. No patients were lost to follow-up. No significant difference was found between the two arms for the end points of local relapse-free rate (p = 0.91), regional relapse-free rate (p = 0.17, adjusted) or overall survival (p = 0.86). Eight-eight patients had attempted surgical resection following radiotherapy failure. The contribution of salvage surgery to overall survival was similar for both arms of the study as was the surgical complication rate. Serious late radiation toxicity was minimal (3% in the RT group, 0% in the radiation therapy plus chemotherapy group). The result of the trial shows no advantage in terms of local control or survival for the experimental treatment arm of split course radiotherapy and concurrent chemotherapy with Mitomycin C and 5 Fluorouracil compared to radiotherapy alone.

Adenocarcinoma of the rectum treated by radical external radiation therapy.

PURPOSE: To assess the long-term survival and response rates of patients with primary rectal cancer to radical radiation therapy. METHODS AND MATERIALS: Between 1978 and 1987, 229 patients were treated at the Princess Margaret Hospital with radical external radiation therapy for adenocarcinoma of the rectum. Patients were treated with radiation either because they were considered to have unresectable tumors, were medically unfit, or refused surgery, or for a combination of these factors. Doses ranged from 40 Gy in 10 fractions by a split course over 6 weeks to 60 Gy in 30 fractions in 6 weeks. The most commonly prescribed treatment was 52 Gy target absorbed dose in 20 daily fractions over 4 weeks. RESULTS: The overall 5-year actuarial survival rate was 27%; for patients with mobile tumors, it was 48%, partially fixed 27%, and fixed tumor 4%. Forty-eight of the 97 patients (50%) with mobile tumors, 11 of the 37 patients (30%) with partially fixed tumors, and 7 of the 77 patients (9%) with fixed tumors had clinically complete tumor regression following radiation. Of these, 18 of the mobile, 6 of the partially fixed, and 5 of the fixed tumors later relapsed locally. Fifty patients had salvage surgery after failing to achieve complete remission or for local relapse, with a 5-year actuarial survival rate of 42% from the time of surgery. CONCLUSION: Although radiation therapy can cure some patients with mobile or partially fixed rectal adenocarcinomas who refuse or are unsuitable for surgery, local control remains a problem; salvage surgery should be considered in patients who relapse or fail to go into complete remission and who are fit to undergo surgery. For patients with fixed rectal cancers, high-dose external-beam radiation should be part of a planned preoperative regimen or be palliative in intent.

Supraglottic laryngeal carcinoma: an analysis of dose-time-volume factors in 410 patients.

Four hundred and ten patients with supraglottic laryngeal carcinoma treated with moderate dose radical radiotherapy with surgery for salvage (RRSS) were analyzed in detail to determine optimal dose-time-volume parameters to be used in the treatment of each stage of supraglottic carcinoma. In the RRSS group 41% are alive and well at 5 years, 38% died of their tumor and 21% of intercurrent disease. Presence or absence of nodal disease has a major impact on survival. Local control is approximately 70% in T1, T2N0 patients and approximately 50% in T3 and T4N0 patients. Seventeen percent of T1 and T2N0 patients failed in the initially negative neck. Ten major complications (2.4%) have been seen. Local control by irradiation was not influenced by dose or field size. Regional control in the initially negative neck was markedly increased with the use of larger irradiation field sizes. Field sizes of less than 7 X 7 cm resulted in an 18% neck failure rate as compared to 3% with larger field sizes (p = 0.00005). This particularly applied to early stage disease. As a result of the use of larger irradiation field sizes giving reduced neck failure rates, improvement in survival has been seen in early stage supraglottic patients. The results are compared with published results. There is no statistically significant dose response curve in any stage of supraglottic cancer over the dose range 1650-2300 ret. Optimal treatment factors for supraglottic cancer are discussed.

Carcinoma of the hypopharynx results of primary radical radiation therapy.

The results of radiation therapy as applied to patients with squamous cell carcinoma of the hypopharynx seen during the period 1972-1976 at the Princess Margaret Hospital are presented. Approximately 2/3 of the patient population presented with disease involving the regional lymph nodes or with systemic metastases. Ninety percent (127/141) of all patients registered were treated primarily with radiation therapy with surgery reserved for the management of residual or recurrent disease only. Seventy-seven percent (98/127) of those who received radiation therapy were treated with radical intent. The uncorrected actuarial 5 year survival rate for those patients treated radically was 19%. Five year actuarial survival rates by the UICC TNM (1974) staging system, showed that nodal disease was the most significant determinant of survival. Five year survival rates were as follows: N0 36%; N1 20%; N2N30%. When considered within each nodal category the survival of the combined T1T2 group was not significantly different from the T3 category. Forty-five percent of those patients who failed with local or regional disease had an attempt at salvage surgery. Of these, 6/24 ultimately achieved local and regional control. Comparisons with other series in the literature are discussed and reasons for differences in published results are considered.

T1/T2 glottic cancer managed by external beam radiotherapy: the influence of pretreatment hemoglobin on local control.

PURPOSE: Pretreatment hemoglobin (Hb) level has been reported to be an important prognostic factor for local control and survival in various malignancies. However, in many settings, the adverse effect of a low Hb may be related to more advanced disease. The purpose of this analysis was to assess the influence of pretreatment Hb on local control in a large series of patients with a localized cancer (T1/T2 glottic cancer, AJCC 1992) treated in a standard fashion. MATERIALS AND METHODS: Between January 1981 and December 1989, 735 patients (median age 63; 657 males, 78 females) with T1/T2 glottic cancer were treated with radiation therapy (RT). The standard RT prescription was 50 Gy in 20 fractions over 4 weeks (97% of patients). Factors studied for prognostic importance for local failure included pretreatment Hb, age, sex, T category, anterior commissure involvement, subglottic extension, and tumor bulk (presence of visible tumor vs. subclinical disease). RESULTS: With a median follow-up of 6.8 years (range 0.2-14.3), 131 patients have locally relapsed for an actuarial 5-year relapse-free rate of 81.7%. The 5-year actuarial survival was 75.8%. The mean pretreatment hemoglobin level was 14.8 g/dl and was similar in all prognostic categories. On multivariate analysis, using the Cox proportional hazards model, pretreatment Hb predicted for local failure after RT. The hazard ratio (HR) for relapse was calculated for various Hb levels. For example, the HR for a Hb of 12 g/dl vs. a Hb of 15 g/dl was 1.8 (95% confidence interval 1.2-2.5). Previously established factors, including gender, T category, subglottic extension, as well as tumor bulk, were also prognostically important for local control. CONCLUSIONS: This analysis, in a large number of similarly treated patients, indicates that pretreatment Hb is an independent prognostic factor for local control in patients with T1/T2 carcinoma of the glottis treated with RT. The underlying biology of this observation needs to be explored, and using this information, it may be possible to develop strategies to improve treatment outcome.

Similar decreases in local tumor control are calculated for treatment protraction and for interruptions in the radiotherapy of carcinoma of the larynx in four centers.

PURPOSE: Data on patients with cancer of the larynx are analyzed using statistical models to estimate the effect of gaps in the treatment time on the local control of the tumor. METHODS AND MATERIALS: Patients from four centers, Edinburgh, Glasgow, Manchester, and Toronto, with carcinoma of the larynx and treated by radiotherapy were followed up and the disease-free period recorded. In all centers the end point was control of the primary tumor after irradiation alone. The local control rates at > or = 2 years, Pc, were analyzed by log linear models, and Cox proportional hazard models were used to model the disease-free period. RESULTS: T stage, nodal involvement, and site of the tumor were important determinants of the disease-free interval, as was the radiation schedule used. Elongation of the treatment time by 1 day, or a gap of 1 day, was associated with a decrease in Pc of 0.68% per day for Pc = 0.80, with a 95% confidence interval of (0.28, 1.08)%. An increase of 5 days was associated with a 3.5% reduction in Pc from 0.80 to 0.77. At Pc = 0.60 an increase of 5 days was associated with an 7.9% decrease in Pc. The time factor in the Linear Quadratic model, gamma/alpha, was estimated as 0.89 Gy/day, 95% confidence interval (0.35, 1.43) Gy/day. CONCLUSIONS: Any gaps (public holidays are the majority) in the treatment schedule have the same deleterious effect on the disease free period as an increase in the prescribed treatment time. For a schedule, where dose and fraction number are specified, any gap in treatment is potentially damaging.

Radiation-induced lung damage: dose-time-fractionation considerations.

The comparison of different dose-time-fractionation schedules requires the use of an isoeffect formula. In recent years, the NSD isoeffect formula has been heavily criticized. In this report, we consider an isoeffect formula which is specifically developed for radiation-induced lung damage. The formula is based on the linear-quadratic model and includes a factor for overall treatment time. The proposed procedures allow for the simultaneous derivation of an alpha/beta ratio and a gamma/beta time factor. From animal data in the literature, the derived alpha/beta and gamma/beta ratios for acute lung damage are 5.0 +/- 1.0 Gy and 2.7 +/- 1.4 Gy2/day respectively, while for late damage the suggested values are 2.0 Gy and 0.0 Gy2/day. Data from two clinical studies, one prospective and the other retrospective, were also analysed and corresponding alpha/beta and gamma/beta ratios were determined. For the prospective clinical study, with a limited range of doses per fraction, the resultant alpha/beta and gamma/beta ratios were 0.9 +/- 2.6 Gy and 2.6 +/- 2.5 Gy2/day. The combination of the retrospective and prospective data yielded alpha/beta and gamma/beta ratios of 3.3 +/- 1.5 Gy and 2.4 +/- 1.5 Gy2/day, respectively. One potential advantage of this isoeffect formalism is that it might possibly be applied to both acute and late lung damage. The results of this formulation for acute lung damage indicate that time-dependent effects such as slow repair or proliferation might be more important in determining isoeffect doses than previously predicted by the estimated single dose (ED) formula. Although we present this as an alternative approach, we would caution against its clinical use until its applicability has been confirmed by additional clinical data.

The effect of treatment duration in the local control of cervix cancer.

A significant effect of treatment duration on pelvic control was found in 830 patients with cervix cancer treated by radical radiation therapy. Using three methods of analysis, the loss of control consistently approximated 1% per day of treatment prolongation beyond 30 days, although analysis of stage subgroups showed that this effect was predominantly manifested in Stages III/IV compared with Stages I/II. In multivariate analyses using both a logistic regression and a Cox regression model, stage (p = 0.0001 for Stage I/IIA and 0.0036 for Stage IIB relative to Stage III/IV) treatment time (p = 0.0001), and age (p = 0.0067) were independently correlated with pelvic control. Exclusion from analysis of patients with delays due to tumour or treatment related complications, intercurrent illness or manifestations of poor tumour response did not significantly change the magnitude of the time effect nor the ranking of the significant covariates. These results are consistent with the occurrence of accelerated repopulation and warrant further investigation, preferably in a randomized trial of accelerated versus conventionally fractionated radiation therapy.

The effect of treatment time and treatment interruption on tumour control following radical radiotherapy of laryngeal cancer.

A significant effect of overall treatment time on local control was found in a retrospective review of 1012 radically irradiated squamous cell carcinomas of the larynx. The actuarial local relapse free rate (LRFR) at 5 years for the whole group was 59%. The effect of treatment time on local control was modelled to the linear-quadratic equation. Using logistic regression analysis treatment time and dose were significant (p = 0.008 and p = 0.04, respectively). When the analysis was adjusted for the influence of stage and laryngeal subsite treatment time remained a significant prognostic factor (p = 0.02). The derived value of gamma/alpha was 0.7 Gy/day and when adjusted for stage and sub-site 0.8 Gy/day. This equates to a dose increment to maintain iso-effective local control of 0.64 Gy/day and 0.73 Gy/day respectively for daily fractions of 2.5 Gy and an assumed alpha/beta for tumour of 25 Gy. To provide an estimate of the clinical impact of treatment interruptions not compensated for by dose escalation a Cox regression was performed. Significant variables were T stage, N stage, sex, total dose and total length of treatment interruption. Using the proportional hazard model it was calculated that each day of treatment interruption resulted in an increase in the hazard of local relapse by 4.8% (p = 0.006). Based on our data it was calculated that this would result in a decrease in local control of 1.4% for each day of uncompensated treatment interruption.

Results of external beam irradiation for rectal carcinomas locally recurrent after local excision or electrocoagulation.

The outcome of 42 patients who developed locally recurrent rectal carcinoma after initial local excision or electrocoagulation was presented. Five patients received combined surgery and radiotherapy (XRT). The remaining 37 patients were managed by XRT alone. The overall 5 year actuarial survival and local control rates were 21 and 22%, respectively. For patients who received XRT alone, the 5 year actuarial survival and local control rates were 20 and 15%, respectively. The corresponding figures were 35 and 40% for patients who received a total XRT dose of 50 Gy or more. One patient who underwent combined treatment developed rectal and bladder incontinence requiring surgery. For patients with rectal recurrence after initial conservative surgery, XRT is an alternative to abdominoperineal resection if major surgical resection is contraindicated.

Total abdominal irradiation for cancer of the colon.

A retrospective analysis of 55 patients treated with whole abdominal irradiation following surgical excision for cancer of the colon is presented. Three groups of patients were given whole abdominal irradiation, eight with gross residual tumor following surgery, 17 with peritoneal seeding, and 30 who had complete surgical excision of the tumor but were felt to be at high risk for relapse. Only one of the eight patients with gross residual tumor, and one of the 17 with peritoneal metastases, are currently alive and well, with the majority dying from local or peritoneal metastases. The 5 year actuarial survival for the 30 patients irradiated following complete surgical excision is 55%. The treatment was well tolerated and few complications were observed. It is concluded that whole abdominal irradiation is ineffective for the treatment of colon cancer if peritoneal metastases are present, or if gross residual tumor is left behind following surgery. A randomized controlled clinical trial is being organized to test whether total abdominal irradiation is of benefit in terms of survival in high risk colon cancer patients following complete surgical removal.

Radical radiation therapy with 5-fluorouracil infusion and mitomycin C for oesophageal squamous carcinoma.

Thirty-five patients with clinically staged non-metastatic squamous carcinoma of the oesophagus were treated with radiation combined with mitomycin C, and 5-fluorouracil (5-FUra) infusion. Twenty patients were planned for a split course regimen 2250-2500 cGy in 10 fractions and chemotherapy. This dose of radiation to be repeated with another course of chemotherapy after 4 weeks rest. Fifteen patients were planned for a single course 4500-5000 cGy in 20 fractions and a single course of chemotherapy. Thirty-one patients are available for a minimum follow-up of one year, 26 patients for a minimum follow-up of 2 years. All 35 patients are included in the survival and local relapse-free analysis. Survival at one year is 47% and at 2 years 28%. The local relapse-free rate at both one and 2 years is 48%. There was an improvement in survival and local relapse-free rate for the single course regimen compared to the split course; 2 years survival 48% versus 12% (p = 0.24) local relapse-free rate 79% versus 27% (p = 0.07). All patients receiving radiation and chemotherapy were compared with historical controls treated by radiation alone. This matching procedure was done independent of knowledge of outcome (two controls were matched/case). Patients were matched for age, sex. TNM stage, and total radiation dose. There was a significant difference in survival p = 0.004 and local relapse-free rate p = 0.05 for patients receiving radiation and chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of radiotherapy treatment time on control of laryngeal cancer: comparisons between centres in Manchester, UK and Toronto, Canada.

A comparison has been made of the influence of treatment time on tumour control rates for 496 (T2 and T3) larynx cancer cases in Manchester, UK and 1001 (T1-T4) cases in Toronto, Canada. Both series of patients were treated in fairly short overall times, commonly 3 weeks in Manchester and 4-5 weeks in Toronto. All the tumour control data were analysed using the same method to obtain values of fitted dose, fractionation and time parameters. The analysis showed the following. (a) Differences between the total combined (T2 + T3) data sets from the two centres, fitted using direct analysis and the LQ model incorporating a parameter for overall treatment time, were not significant (p = 0.17) and close similarity in control rates was observed using treatment regimens common to both series. (b) The Manchester series over 9-41 days and the Toronto series over 14-84 days are both consistent in showing for (T2 + T3) tumours the presence of a mean time factor of 0.6-0.8 Gy/day required to abrogate the decrease in tumour control concomitant with an increase in overall treatment time from the minimum the maximum employed in each series. (c) When a parameter was included in the model to test for the possible presence of a lag period before the time factor became operative, the lag was not significant for the Toronto data, in contrast to a significant lag for the Manchester data alone (T2 + T3 data).(ABSTRACT TRUNCATED AT 250 WORDS)