Understanding the potential for efficient triplet harvesting with hot excitons.

Excited state energy transfer in disordered systems has attracted significant attention owing to the importance of this phenomenon in both artificial and natural systems that operate in electronically excited states. Of particular interest, especially in the context of organic electronics, is the dynamics of triplet excited states. Due to their weak coupling to the singlet manifold they can often act as low energy trapping sites and are therefore detrimental to device performance. Alternatively, by virtue of their long lifetime they can lead to enhanced diffusion lengths important for organic photovoltaics (OPV). Herein, we explore the triplet energy transfer mechanism from dichlorobenzene to thioxanthone in methanol solution. We rationalise previous experimental observations as arising from preferential population transfer into the lowest triplet state rather than the higher lying triplet state that is closer in energy. The reason for this is a delicate balance between the electronic coupling, reorganisation energy and the energy gap involved. The present results provide the understanding to potentially develop a hot exciton mechanism in materials for organic light emitting diodes (OLED) to achieve higher device efficiencies.

Alcohol use and mental health symptoms in female firefighter recruits.

BACKGROUND: Limited research suggests that female firefighters report problem drinking at higher rates than the general population. AIMS: To identify longitudinal drinking patterns in female firefighters, make comparisons to male firefighters and examine problem drinking in relation to post-traumatic stress disorder (PTSD) and depression. METHODS: Study participants included 33 female and 289 male firefighter recruits, who were assessed over their first 3 years of fire service. RESULTS: Female firefighters consumed increasing numbers of drinks per week, with a median of 0.90 drinks per week at baseline, and 1.27 drinks in year 3. Female firefighters reported binge drinking at high rates, with nearly half binging at least once per year across all time points (44-74%). The percentage that reported binge drinking three or more times per month doubled over the course of the study (from 9% to 18%). Overall, males reported higher rates of binge drinking and a greater number of drinks per week; however, binge drinking rates among females increased over time and became comparable to rates of binge drinking among males. A greater percentage of female than male firefighters met the criteria for problem drinking by year 1. Problem drinking was associated with screening positive for PTSD at year 1 and depression at year 2, but not with occupational injury. CONCLUSIONS: Over time, female firefighters reported increasing amounts of drinking, more frequent binge drinking and more negative consequences from drinking. These findings along with existing literature indicate female firefighters change their drinking in the direction of their male counterparts.

Longitudinal associations between post-traumatic stress disorder and metabolic syndrome severity.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with elevated risk for metabolic syndrome (MetS). However, the direction of this association is not yet established, as most prior studies employed cross-sectional designs. The primary goal of this study was to evaluate bidirectional associations between PTSD and MetS using a longitudinal design. METHOD: A total of 1355 male and female veterans of the conflicts in Iraq and Afghanistan underwent PTSD diagnostic assessments and their biometric profiles pertaining to MetS were extracted from the electronic medical record at two time points (spanning ~2.5 years, n = 971 at time 2). RESULTS: The prevalence of MetS among veterans with PTSD was just under 40% at both time points and was significantly greater than that for veterans without PTSD; the prevalence of MetS among those with PTSD was also elevated relative to age-matched population estimates. Cross-lagged panel models revealed that PTSD severity predicted subsequent increases in MetS severity (ß = 0.08, p = 0.002), after controlling for initial MetS severity, but MetS did not predict later PTSD symptoms. Logistic regression results suggested that for every 10 PTSD symptoms endorsed at time 1, the odds of a subsequent MetS diagnosis increased by 56%. CONCLUSIONS: Results highlight the substantial cardiometabolic concerns of young veterans with PTSD and raise the possibility that PTSD may predispose individuals to accelerated aging, in part, manifested clinically as MetS. This demonstrates the need to identify those with PTSD at greatest risk for MetS and to develop interventions that improve both conditions.

The genome of the simian and human malaria parasite Plasmodium knowlesi.

Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome and other sequenced Plasmodium genomes. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.

Glucocorticoid-induced hyperglycemia is prevalent and unpredictable for patients undergoing cancer therapy: an observational cohort study.

BACKGROUND: Patients with cancer are often treated with glucocorticoids (gcs) as part of therapy, which may cause hyperglycemia. We sought to define the prevalence of, and risk factors for, hyperglycemia in this setting. METHODS: Adult patients taking gc as part of therapy protocols for primary brain tumour or metastasis, for lymphoma, or for bone marrow transplant (bmt) were screened with random glucometer measurements taken at least 3 hours after the last dose gcs. RESULTS: We screened 90 patients [44.4% women, 55.6% men; mean age: 59.6 years (range: 25-82 years); mean body mass index (bmi): 26.4 kg/m(2) (range: 15.8-45.3 kg/m(2))] receiving gc as part of cancer treatment. Mean total daily gc dose in the group was 238.5 mg (range: 30-1067 mg) hydrocortisone equivalents. Hyperglycemia (glucose ≥ 8.0 mmol/L) was found in 58.9% (53 of 90), and diabetes mellitus (dm)-range hyperglycemia (glucose ≥ 11.1 mmol/L) in 18.9% (17 of 90). The mean time from gc ingestion to glucometer testing was 5.5 hours (range: 3-20 hours). Presence of hyperglycemia did not correlate with traditional dm risk factors such as age, sex, bmi, and personal or family history of dm. A longer interval from gc dose to testing (p < 0.05), a higher gc dose (p = 0.04), and a shorter interval between the preceding meal and testing (p = 0.02) were risk factors for hyperglycemia in some patient groups. CONCLUSIONS: Glucocorticoid-induced hyperglycemia is common in patients undergoing cancer treatment and cannot be predicted by traditional risk factors for dm. We recommend that all cancer patients receiving gc be screened for hyperglycemia at least 4-6 hours after gc administration.

Androgen deprivation therapy: past, present and future.

Since Huggins and Hodges demonstrated the responsiveness of prostate cancer to androgen deprivation therapy (ADT), androgen-suppressing strategies have formed the cornerstone of management of advanced prostate cancer. Approaches to ADT have included orchidectomy, oestrogens, luteinizing hormone-releasing hormone (LHRH) agonists, anti-androgens and more recently the gonadotrophin-releasing hormone antagonists. The most extensively studied antagonist, degarelix, avoids the testosterone surge and clinical flare associated with LHRH agonists, offering more rapid PSA and testosterone suppression, improved testosterone control and improved PSA progression-free survival compared with agonists. The clinical profile of degarelix appears to make it a particularly suitable therapeutic option for certain subgroups of patients, including those with metastatic disease, high baseline PSA (>20 ng/mL) and highly symptomatic disease. As well as forming the mainstay of treatment for advanced prostate cancer, ADT is increasingly used in earlier disease stages. While data from clinical trials support the use of ADT neoadjuvant/adjuvant to radiotherapy for locally advanced or high-risk localized prostate cancer, it remains to be established whether specific ADT classes/agents provide particular benefits in this clinical setting.

FSH suppression and tumour control in patients with prostate cancer during androgen deprivation with a GnRH agonist or antagonist.

BACKGROUND: Gonadotropin releasing hormone (GnRH) antagonists suppress follicle-stimulating hormone (FSH) to lower levels than GnRH agonists. This may partially explain the differences between these agents on prostate cancer outcomes. In this post-hoc analysis, FSH and prostate specific antigen (PSA) responses and the impact of cross-over from leuprolide to degarelix were evaluated from a 1-year comparative study (CS21) and its extension study (CS21A). MATERIALS AND METHODS: Overall, 610 patients were enrolled in CS21, wherein PSA and FSH levels were evaluated monthly. CS21A evaluated 386 patients, including those previously treated with degarelix (n = 251) who continued to receive degarelix, and those previously treated with leuprolide (n = 135) who crossed-over to receive degarelix. PSA and FSH levels were evaluated in CS21A for 3 months after cross-over. The associations between measurements were assessed using Spearman's correlation coefficient. The impact of class variables on FSH suppression were evaluated using Analysis of Variance. RESULTS: Rapid PSA and FSH suppression was observed and maintained in the degarelix arm (CS21 and CS21A), while patients on leuprolide experienced rising PSA during CS21. Patients crossed-over from leuprolide to degarelix achieved a suppression of FSH and a significant PSA decrease. PSA and FSH levels were significantly (p < .05) correlated at months 1, 3, 6, 12 and 13 in the degarelix arm. CONCLUSIONS: Significant FSH suppression with GnRH antagonists may explain its advantage over GnRH agonists in terms of better prostate cancer control. The effect of profound FSH suppression is analogous to the need for profound testosterone suppression for tumor control.

Combination versus single agent therapy in effecting complete therapeutic response in human bladder cancer: analysis of cisplatin and/or 5-fluorouracil in an in vivo survival model.

An in vivo study of cisplatin (CDDP) and 5-fluorouracil (5FU) cytotoxicity was performed using a multidose matrix with a human bladder transitional cell carcinoma xenograft tumor line (DU4284) tested by subrenal capsule assay in 154 nude mice (NM-SRCA). Statistical analysis of initial growth inhibition at 20 days and host survival demonstrates therapeutic, cooperative interaction. Toxic doses of either CDDP or 5FU alone as well as low-dose combinations provided modest or no survival benefit. The single dose of CDDP (7 mg/kg) and of 5FU (100 mg/kg) was best (by analysis of efficacy and toxicity) of those tested and caused > 97% initial regression. While 94% of controls incurred tumor deaths by 225 days, 75% treated at this dose were tumor free and likely cured. Our conclusions were: (a) NM-SRCA human xenograft testing is excellent for rapid in vivo screening of promising treatment strategies to evaluate for efficacy at acceptable toxicity, but confirmation of true therapeutic impact should be sought by correlating initial growth inhibition with host survival; (b) enhanced survival seen only when CDDP/5FU are used together (versus either single agent) supports the value of pursuing histiotype-specific screening of potentially synergistic drug combinations; and (c) of clinical relevance, human transitional cell carcinoma is now identified as a histiotype in which a therapeutic, cooperative interaction between CDDP/5FU has been demonstrated in vivo.

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.

Psychometric detection of fabricated symptoms of posttraumatic stress disorder.

Vietnam veterans with posttraumatic stress disorder and two groups instructed to fabricate its symptoms completed the MMPI. A discriminant function analysis of selected scale scores and an empirically derived decision rule successfully classified over 90% of the subjects.

Acute radiation-induced pulmonary damage: a clinical study on the response to fractionated radiation therapy.

Acute radiation-induced pulmonary damage can be a significant cause of morbidity in radiation therapy of the thorax. A prospective, clinical study was conducted to obtain dose-response data on acute pulmonary damage caused by fractionated radiation therapy. The endpoint was a visible increase in lung density within the irradiated volume on a computed tomographic (CT) examination as observed independently by three diagnostic radiologists. Fifty-four patients with various malignancies of the thorax completed the study. CT chest scans were taken before and at preselected times following radiotherapy. To represent different fractionation schedules of equivalent biological effect, the estimated single dose (ED) model, ED = D X N-0.377 X T-0.058 was used in which D was the average lung dose within the high dose region in cGy, N was the number of fractions, and T was the overall treatment time in days. Patients were grouped according to ED and the percent incidence of pulmonary damage for each group was determined. Total average lung doses ranged from 29.8 Gy to 53.6 Gy given in 10 to 30 fractions over a range of 12 to 60 days. Five patient groups with incidence ranging from 30% (ED of 930) to 90% (ED of 1150) were obtained. The resulting dose-response curve predicted a 50% incidence level at an ED value (ED50) of 1000 +/- 40 ED units. This value represents fractionation schedules equivalent to a total average lung dose of 32.9 Gy given in 15 fractions over 19 days. Over the linear portion of the dose-response curve, a 5% increase in ED (or total dose if N and T remain constant), predicts a 12% increase in the incidence of acute radiation-induced pulmonary damage.

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%.

Enhanced control by radiotherapy of cervical lymph node metastases arising from nasopharyngeal carcinoma compared with nodal metastases from other head and neck squamous cell carcinomas.

PURPOSE: To test the hypothesis that metastatic cervical lymph nodes arising from nasopharyngeal carcinoma (NPC) are more readily controlled with radiotherapy than comparable nodes from squamous cell carcinomas of other head and neck sites (SCC). METHODS AND MATERIALS: One hundred four NPC patients with metastatic cervical nodes (mean size of the largest node equals 4.1 cm) were randomly selected from radiation treatment files for two time periods, 1969-1976 and 1983-1988, when radiation alone was the first line treatment. Candidate controls were selected randomly from radiation treatment files of node positive squamous cell carcinomas arising from the oropharynx, hypopharynx, oral cavity or larynx who were also treated by radical radiation therapy as sole initial treatment in the 1970s and 1980s. Each NPC case was matched with a control using the size of the largest involved node as the matching criterion. The median follow-up of all 208 patients was 3 years (4.2 years in NPC cases and 1.4 years in the matched controls). For those who were alive at last follow-up, the median follow-up for both arms was 7.7 years (6.7 years in NPC cases and 10.2 years in the matched controls). Nodal control was evaluated by clinical neck examination in both arms. Nodal recurrence was defined as relapse or persistence of metastatic nodal disease from day 1 of radiotherapy treatment. RESULTS: Despite a similar mean delivered dose to involved neck nodes (52.9 Gy for the NPC group and 53.9 Gy for the matched controls), the SCC group had significantly worse nodal control with radiation when compared to the NPC group (p < 0.0001, relative risk 3.0, 95% [1.8, 5.1]). The 3-year nodal recurrence-free rate among NPC cases was 71 +/- 5%, compared to 43 +/- 5% among matched controls. CONCLUSION: The result of this study supports the hypothesis that metastatic cervical nodes from NPC are more readily controlled by irradiation than cervical nodes of similar size arising from other head and neck squamous cell carcinomas. Further study is required to explore the reasons for this apparent radiosensitivity.

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.

Outcome following radiotherapy in verrucous carcinoma of the larynx.

PURPOSE: To evaluate the outcome of patients with verrucous carcinoma of the larynx treated at the Princess Margaret Hospital with respect to control rates with radiotherapy, the salvage of local failure, the risk of regional lymph node metastasis following radiation therapy, and the risk of anaplastic transformation following radiotherapy. METHODS AND MATERIALS: Forty-eight patients underwent primary treatment for verrucous carcinoma of the larynx in the period between January 1961 and December 1990. This represented 1.1% of cases of laryngeal cancer seen in this time period. Forty-three received radiotherapy and 5 had surgery as the primary treatment. Several radiation dose-fractionation schedules were used, the most frequent being 50 Gy in 20 fractions in 4 weeks (31 cases), while eight patients were treated with 55 Gy over 5 weeks. RESULTS: The 5-year rate of local control was 59% for the 43 patients treated with radiotherapy. Surgical salvage was universally successful in all cases where it was attempted. The five cases treated with surgery alone did not experience relapse. Only one patient died of verrucous carcinoma. He had been medically unfit for surgical intervention at the time of initial treatment and at the time of relapse. He underwent a truncated course of radiotherapy (24 Gy in 3 fractions over three weeks in 1975). There was no evidence of increased neck relapse compared to other forms of laryngeal carcinoma following radiation treatment. No evidence to support anaplastic transformation of tumors treated with radiotherapy was evident in this series. CONCLUSIONS: Local control using radiation treatment is less successful than with ordinary invasive and in situ squamous carcinomas of the larynx. Nevertheless, the treatment is effective and provides an appropriate option for laryngeal conservation, especially in advanced lesions where total laryngectomy may be the only treatment alternative. Surgical salvage of radiation failures contributes to very high rates of cure for verrucous carcinoma of the larynx. Anaplastic transformation of cases treated with radiotherapy was not observed in any case in this series.

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.

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.

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.

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.