Evaluating an equity-focused approach to assess climate resilience and disaster priorities through a community survey.

As the Duwamish Valley community in Seattle, Washington, U.S.A. and other environmental justice communities nationally contend with growing risks from climate change, there have been calls for a more community-centered approach to understanding impacts and priorities to inform resilience planning. To engage community members and identify climate justice and resilience priorities, a partnership of community leaders, government-based practitioners, and academics co-produced a survey instrument and collected data from the community using the Seattle Assessment for Public Health Emergency Response (SASPER), an approach adapted from the Centers for Disease Control and Prevention's Community Assessment for Public Health Emergency Response (CASPER). In addition, we conducted a process and outcome project evaluation using quantitative survey data collected from volunteers and qualitative semi-structured interviews with project team members. In October and November 2022, teams of volunteers from partner organizations collected 162 surveys from households in the Duwamish Valley. Poor air quality, extreme heat, and wildfires were among the highest reported hazards of concern. Most Duwamish Valley households agreed or strongly agreed that their neighborhood has a strong sense of community (64%) and that they have people nearby to call when they need help (69%). Forty-seven percent of households indicated willingness to get involved with resilience planning, and 62% of households said that they would use a Resilience Hub during an emergency. Survey volunteers evaluated their participation positively, with over 85% agreeing or strongly agreeing that they learned new skills, were prepared for the survey, and would participate in future assessments. The evaluation interviews underscored that while the SASPER may have demonstrated feasibility in a pre-disaster phase, CASPER may not meet all community/partner needs in the immediate disaster response phase because of its lack of focus on equity and logistical requirements. Future research should focus on identifying less resource intensive data collection approaches that maintain the rigor and reputation of CASPER while enabling a focus on equity.

Cumulative Impacts and COVID-19: Implications for Low-Income, Minoritized, and Health-Compromised Communities in King County, WA.

Few studies have assessed how the intersection of social determinants of health and environmental hazards contributes to racial disparities in COVID-19. The aim of our study was to compare COVID-19 disparities in testing and positivity to cumulative environmental health impacts, and to assess how unique social and environmental determinants of health relate to COVID-19 positivity in Seattle, King County, WA, at the census tract level. Publicly available data (n = 397 census tracts) were obtained from Public Health-Seattle & King County, 2018 ACS 5-year estimates, and the Washington Tracking Network. COVID-19 testing and positive case rates as of July 12, 2020, were mapped and compared to Washington State Environmental Health Disparities (EHD) Map cumulative impact rankings. We calculated odds ratios from a series of univariable and multivariable logistic regression analyses using cumulative impact rankings, and community-level socioeconomic, health, and environmental factors as predictors and having ≥ 10% or < 10% census tract positivity as the binary outcome variable. We found a remarkable overlap between Washington EHD cumulative impact rankings and COVID-19 positivity in King County. Census tracts with ≥ 10 % COVID-19 positivity had significantly lower COVID-19 testing rates and higher proportions of people of color and faced a combination of low socioeconomic status-related outcomes, poor community health outcomes, and significantly higher concentrations of fine particulate matter (PM2.5). King County communities experiencing high rates of COVID-19 face a disproportionate cumulative burden of environmental and social inequities. Cumulative environmental health impacts should therefore systematically be considered when assessing for risk of exposure to and health complications resulting from COVID-19.

Community-Level Factors Associated with COVID-19 Cases and Testing Equity in King County, Washington.

Individual-level Coronavirus Disease 2019 (COVID-19) case data suggest that certain populations may be more impacted by the pandemic. However, few studies have considered the communities from which positive cases are prevalent, and the variations in testing rates between communities. In this study, we assessed community factors that were associated with COVID-19 testing and test positivity at the census tract level for the Seattle, King County, Washington region at the summer peak of infection in July 2020. Multivariate Poisson regression was used to estimate confirmed case counts, adjusted for testing numbers, which were associated with socioeconomic status (SES) indicators such as poverty, educational attainment, transportation cost, as well as with communities with high proportions of people of color. Multivariate models were also used to examine factors associated with testing rates, and found disparities in testing for communities of color and communities with transportation cost barriers. These results demonstrate the ability to identify tract-level indicators of COVID-19 risk and specific communities that are most vulnerable to COVID-19 infection, as well as highlight the ongoing need to ensure access to disease control resources, including information and education, testing, and future vaccination programs in low-SES and highly diverse communities.

Is there a limit to dose escalation for rectal cancer?

The radiation tolerance of the rectum is not fully understood. Published studies on the radiation treatment of cancers of the prostate, cervix and rectum have been reviewed to determine currently recommended dose-volume guidelines. The need for further studies directed specifically at the treatment of primary rectal cancer and perirectal node metastases is discussed. There seems to be room for escalation of the external beam doses currently given.

Does a centralized radiotherapy system provide adequate access to care?

PURPOSE: In the Canadian province of Ontario, all radiotherapy is provided by a centrally managed provincial network of nine cancer centers. The primary goal of this study was to determine whether this highly centralized radiotherapy system provides adequate and equitable access to care for the province's dispersed population. METHODS: The Ontario Cancer Registry (OCR) was used to identify 295,386 cases of invasive cancer, excluding nonmelanoma skin cancer, which were diagnosed in Ontario between 1984 and 1991. Electronic radiotherapy records from each of the province's radiotherapy centers were linked to the registry at the level of the individual case. RESULTS: The proportion of incident cases treated with radiotherapy was 18.8% at 4 months after diagnosis, 23.7% at 1 year, 25.8% at 2 years, 28.2% at 5 years, and 29.1% at 8 years. These rates of radiotherapy use are much lower than the accepted national and international targets, and lower than rates reported from other jurisdictions. The rate of radiotherapy use at 1 year varied significantly from county to county across Ontario (range, 18.6% to 32.4%; P < 10(-6)), and the highest rates were recorded in communities close to radiotherapy centers. There was a common geographic pattern of rate variations among several disease groups, including breast cancer, lung cancer, the genitourinary malignancies, and the gastrointestinal malignancies. CONCLUSION: The low and uneven rates of radiotherapy use across the province indicate that Ontario's centralized radiotherapy system does not, at present, provide adequate or equitable access to care.

Beta-amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer's disease.

The relationship between progressive cognitive decline and underlying neuropathology associated with Alzheimer s disease (AD) is a key issue in defining the mechanisms responsible for functional loss. This has been a subject of much controversy, with separate studies comparing various clinical and neuropathological indices in AD. Further, it is difficult to compare studies with differences in histochemical staining protocols, brain regions examined, and data quantification criteria. There are many difficulties in designing a clinical-pathological correlative study involving AD patients. It is necessary to control for several key parameters. For example, a broad range of cognitively impaired subjects is needed, as well as short postmortem delays, brief intervals between cognitive testing and death, and the most sensitive detection and quantification techniques. In this study, we carefully controlled for each of these parameters to determine if there is a relationship between global cognitive dysfunction and multiple neuropathological indices. We selected 20 individuals representing a broad range of cognitive ability from normal to severely impaired based on the MMSE, Blessed IMC, and CDR. We counted plaque number, NFT number, dystrophic neurite number, and the relative extent of thioflavine positive plaques and neuritic involvement within plaques. We also quantified cortical area occupied by beta-amyloid immunoreactivity (A beta Load) and PHF-1 positive neuropil threads and tangles (PHF Load) using computer-based image analysis. Interestingly, we found that most pathologic measures correlated highly with the severity of dementia. However, the strongest predictor of premortem cognitive dysfunction on all three cognitive measures was the relative area of entorhinal cortex occupied by beta-amyloid deposition. In conclusion, our data show that in a carefully controlled correlative study, a variety of neuropathological variables are strongly correlated with cognitive impairment. Plaque related variables may be as strongly related to cognitive dysfunction as other established measures, including synapse loss, cell death and tau hyperphosphorylation, although no correlative study can demonstrate causality.

beta-Amyloid converts an acute phase injury response to chronic injury responses.

As the brain ages, amyloid deposits accumulate and, as these deposits condense into a beta-sheet conformation, they contribute to the organization of cellular responses and maintain a chronic level of stimulation and injury. Furthermore, accompanying reactions can lead to the production of additional beta-amyloid, the build up of additional fibrillar beta-amyloid, and prolongation of the response. As it accumulates, beta-amyloid appears to develop properties that drive many signal transduction processes in the classic injury cascade and also activate complement, which results in an amplified beta-amyloid AD cascade. In this way several mechanisms, although apparently independent, proceed in parallel, reinforce each other, and perpetuate pathology and structural damage to the brain. Specifically, we suggest that via the activation of complement, initiation, and perpetuation of other cascades, and its own direct toxic actions, beta-amyloid converts an acute response to injury into a chronic damaging inflammatory reaction thereby contributing to neuronal dysfunction and degeneration.

Beta-amyloid accumulation in aged canine brain: a model of early plaque formation in Alzheimer's disease.

We characterized eight aged beagles (maintained from birth in a laboratory colony) and one black Labrador using Bielschowsky's, thioflavine S, and Congo red staining, and antibodies to the beta-amyloid peptide, dystrophic neurites, and other plaque components. All plaques within these canine brains were of the diffuse subtype and were neither thioflavine S- nor Congo red-positive. The majority of plaques in the entorhinal cortex contained numerous neurons within them while plaques in the dentate gyrus did not. beta-Amyloid immunoreactivity was also present within select neurons and neuronal processes and was detected as a diffuse linear zone corresponding to the terminal fields of the perforant path. There was no significant correlation between extent of beta-amyloid accumulation and neuron number in entorhinal cortex. Neither tau-1, PHF-1, nor SMI-31-immunostaining revealed dystrophic fibers, confirming the classification of these plaques as diffuse. Canine plaques did not appear to contain bFGF- or HS-positive immunostaining. This may explain why neuritic involvement was not detected within these canine plaques. It is possible that the beta-amyloid within the canine brain has a unique primary structure or may not be in an assembly state that adversely affects neurons.

Analysis of brain injury following intrahippocampal administration of beta-amyloid in streptozotocin-treated rats.

It has been suggested that the vulnerability of the aged brain to Alzheimer's disease (AD) pathogenesis depends on a number of risk factors, including abnormal glycolytic metabolism and beta-amyloid accumulation. Intrahippocampal injections of beta-amyloid and related peptides were administered to chronically hyperglycemic rats to examine beta-amyloid toxicity and the interaction with imbalances of glucose metabolism. Chronic hyperglycemia was induced by systemic injection of streptozotocin (STZ) which selectively destroys pancreatic beta-islet cells. Ten days after intrahippocampal injection of synthetic beta-amyloid peptides (beta 1-42, beta 25-35, scrambled beta 25-35), lesion volume, blood glucose, and plasma corticosterone concentrations, beta 1-42 immunoreactivity and gliosis were assessed to determine peptide toxicity in the normoglycemic and hyperglycemic conditions. Glucose levels correlated with plasma corticosterone concentrations (r = 0.85) and increased lesion volume size (r = 0.36). Intrahippocampal peptide injections in normoglycemic subjects did not induce significant damage as compared to control injections of vehicle alone. STZ-treated groups demonstrated a trend for increased lesion volume size following injection of either vehicle, beta 1-42, or beta 25-35. The combination of the beta 1-42 peptide and streptozotocin-induced hyperglycemia was toxic and induced significantly larger lesions (p < 0.01) of the dorsal blade of the dentate gyrus as compared to injections of beta 1-42 into normoglycemic subjects.

Color image analysis in neuroanatomical research: application to senile plaque subtype quantification in Alzheimer's disease.

Many problems in neuroanatomy and neuropathology require the collection of large data sets and would benefit from a method that allows for rapid quantitative analysis to be carried out on a routine basis. An example is the quantification and subtype classification of the number of senile plaques in post-mortem Alzheimer's disease tissue. A method to reliably automate the analysis of plaques and their underlying subtypes would allow more rigorous and quantitative correlations to be investigated. Computer assisted image analysis of data typically utilizes gray scale images. These methods, however, are only applicable to quantification of objects labeled with a single marker. We sought to extend this type of analysis to double-labeled tissue sections so we could quantify dual labels separately based on their peroxidase color characteristics, analyze the resultant occurrence of overlap between the two labels, and classify senile plaques into discrete subtypes. We present a method for semi-automated color image analysis which allows one to identify separate labels based on histogram mapping of hue, saturation and value as well as apply overlapping feature detection algorithms. The technique is application driven, so that a trained observer can set threshold or object criteria and verify the desired results. These methods were able to yield total "amyloid load" and "dystrophic neurite load" values, generate plaque histograms based on total size, and subtype plaques into diffuse/primitive and neuritic/classical categories. By adjusting feature criteria, we were able to achieve promising agreement (Fisher's R to Z correlation of 0.94) between a human observer and the computer algorithm in the classification of plaque subtypes using three AD cases.

The canine as an animal model of human aging and dementia.

The aged canine displays many features that make it an excellent model for studying the progression of pathology in brain aging and linking these findings to learning, memory and other cognitive functions. Canines develop extensive beta-amyloid deposition within neurons and their synaptic fields, which appears to give rise to senile plaques. These plaques are primarily of the early diffuse subtype. Aged canines also exhibit accumulations of lipofuscin, cerebral vascular changes, dilation of the ventricles, and cytoskeletal changes. Neurofibrillary tangles (NFTs) are not present in the aged canine. Thus, the aged canine brain provides a suitable model for studying early degeneration normally considered to be pre-Alzheimer's. This supposition is also supported by behavioral data. We have found that the extent of beta-amyloid deposition correlates with a decline in select measures of cognitive function. These data provide the first evidence of a correlation between beta-amyloid accumulation and cognitive decline in the absence of NFTs. We summarize four lines of evidence that support using the aged canine as a model of human aging: (a) Aged canines develop aspects of neuropathology similar to that observed in aged humans; (b) Veterinarians have observed that many canines exhibit a clinical syndrome of age-related cognitive dysfunction; (c) Aged canines are deficient on a variety of neuropsychological tests of cognitive function; (d) The level of beta-amyloid accumulation correlates with cognitive dysfunction in the canine. These data indicate that the aged canine is a particularly useful model for studying age-related cognitive dysfunction (ARCD), early neuronal changes associated with aging, and the initial stages of senile plaque formation.

Diffuse plaques contain C-terminal A beta 42 and not A beta 40: evidence from cats and dogs.

Recent reports have suggested that beta-amyloid (A beta) species of variable length C-termini are differentially deposited within early and late-stage plaques and the cerebrovasculature. Specifically, longer C-terminal length A beta 42/3 fragments (i.e., A beta forms extending to residues 42 and/or 43) are thought to be predominant within diffuse plaques while both A beta 42/3 and A beta 40 (A beta forms terminating at residue 40) are present within a subset of neuritic plaques and cerebrovascular deposits. We sought to clarify the issue of differential A beta deposition using aged canines, a partial animal model of Alzheimer's disease that exhibits extensive diffuse plaques and frequent vascular amyloid, but does not contain neuritic plaques or neurofibrillary tangles. We examined the brains of 20 aged canines, 3 aged felines, and 17 humans for the presence of A beta immunoreactive plaques, using antibodies to A beta 1(-17), A beta 17(-24), A beta 1(-28), A beta 40, and A beta 42. We report that plaques within the canine and feline brain are immunopositive for A beta 42 but not A beta 40. This is the first observation of nascent AD pathology in the aged feline brain. Canine plaques also contained epitopes within A beta 1(-17), A beta 17(-24), and A beta 1(-28). In all species examined, vascular deposits were immunopositive for both A beta 40 and A beta 42. In the human brain, diffuse plaques were preferentially A beta 42 immunopositive, while neuritic plaques and vascular deposits were both A beta 40 and A beta 42 immunopositive. However, not all neuritic plaques contain A beta 40 epitopes.

Concomitant radiotherapy and chemotherapy for anal cancer.

Concomitant radiotherapy/chemotherapy is widely used to treat epidermoid cancers of the anal canal. The drugs most frequently combined with radiotherapy are 5-fluorouracil and mitomycin, but other schedules include 5-fluorouracil and cisplatin, 5-fluorouracil alone, or bleomycin alone. Since mechanisms of possible interaction between radiotherapy and the cytotoxic drugs are not well understood, schedules have been developed empirically. Randomized trials comparing radiotherapy/chemotherapy with radical radiotherapy alone have not yet been completed. In nonrandomized studies, however, some drug and radiotherapy combinations appear to be superior to radiotherapy alone. Combined modality therapy has resulted in 5-year survival rates of 65% to 80%; approximately 85% of patients retain anorectal function when the primary tumor is controlled by concomitant radiotherapy/chemotherapy.

Anal cancer.

Combined modality treatment with radiation, chemotherapy, and conservative surgery controls most epidermoid cancers of the anal canal and advanced squamous cell cancers of the perianal skin. Anorectal function is preserved in about 70% of patients or more. Five-year survival rates are similar to those previously obtained with radical surgery or radical radiation therapy. The cytotoxic drugs 5-Fluorouracil and Mitomycin C are frequently given concurrently with radiation, but other effective regimens have also been described. The mechanisms of interaction of radiation and cytotoxic drugs in the treatment of anal cancer are not known.

Radiotherapy for mucosal melanomas.

Twelve patients who were primarily irradiated at the Princess Margaret Hospital (PMH) for mucosal melanomas of the head and neck and 6 patients irradiated for mucosal melanomas of the vagina and anorectal region are reported. The PMH results of irradiation of mucosal melanomas of the head and neck are combined with the literature results for this type of melanoma. A total of 24 patients who had 25 areas irradiated are considered. The complete remission rate locally is 72% (18 of 25 areas treated). Seven of the 18 patients who achieved complete local remission subsequently relapsed locally (9 to 144 months post treatment); 11 are in maintained complete local remission (9 to 54 months). Four died of intercurrent disease without melanoma, 5 are alive and well post irradiation, one recurred regionally and was salvaged surgically and one died of distant metastases without local or regional relapse. Only 1 of 7 patients who failed to respond to irradiation was salvaged with subsequent surgery, the others all died very rapidly following unsuccessful irradiation. Analysis of local control versus fraction size revealed that 6 of 7 patients treated with a fraction size of 400 rad or more achieved complete remission as compared to 5 of 18 treated with a fraction size of 399 rad or less. The results of primary irradiation for mucosal melanomas of the head and neck are compared with the literature on radical surgery, it is concluded that in view of the poor results of radical surgery that large dose per fraction irradiation should be seriously considered as the initial treatment of choice for primary mucosal melanomas of the head and neck. Four patients with vaginal melanomas were treated at the PMH, all achieved complete remission locally, 2 recurred at 18 and 28 months, one is alive and well at 3 years and one died of intercurrent disease at 1 1/2 years. Two patients with anorectal melanoma had transient palliative benefit from irradiation. Since the treatment of both vaginal and thick (greater than 2 mm) anorectal melanoma is essentially palliative it is suggested that irradiation should be considered as an alternate treatment to radical treatment in these conditions.

Local excision and post-operative radiation therapy for rectal carcinoma.

PURPOSE: To assess the patterns of failure and outcome following conservative surgery and post-operative radiation therapy for rectal cancer. METHODS AND MATERIALS: Twenty-five patients underwent post-operative radiation therapy (50 Gy in 20 fractions over 4 weeks) following local excision or electrocoagulation for carcinoma of the rectum. None of the patients had palpable residual disease following surgery. Selection factors for post-operative radiation therapy were refusal of a permanent colostomy, excessive operative risk of an abdominal perineal resection and concern regarding local control with conservative surgery alone. RESULTS: Six of 25 patients developed failure at the primary site. There was no lymph node failure. All five patients with primary failure alone underwent abdominal perineal resection and 2 remained free of recurrence. With a median follow-up of 6 years, 20 of 25 patients remained alive and free of disease. There was no apparent influence of age, sex, type of surgery, tumor size, distance of tumor from anal verge, tumor configuration, resection margins, integrity of the resected tissue, depth of invasion, differentiation, presence of lymphatic or vascular channel invasion, radiation dose or field size on local control and survival. One of 15 patients failed locally when the overall treatment time was 30 days or less, whereas 5 of 10 patients developed local failure when the overall treatment time exceeded 30 days. Sixteen of 20 patients in whom cancer did not recur retained normal anorectal function. All four patients with grade 3 early morbidity and the only patient with Grade 3 late morbidity were amongst the group of 13 patients treated with large AP-PA fields (mean: 15 x 19 cm2). CONCLUSION: In selected patients who are at high risk of local recurrence following local excision alone, and who refuse a colostomy or are at high operative risk from radical surgery, post-operative radiation therapy is an alternative to radical surgery.

Radiotherapy of Kaposi's sarcoma.

Between 1958 and 1983, 91 patients with Kaposi's sarcoma were referred to the Princess Margaret Hospital. Eight patients received no specific therapy immediately following their first assessment. Twenty-seven patients were treated by local field radiotherapy, of whom 17 entered complete remission and 6 have remained relapse-free. Fifty-six patients received extended field radiotherapy, usually a single fraction of 8 Gy megavoltage gamma-ray or photon therapy; 38 achieved completed remission, and 24 have remained relapse-free for a median duration of 3 years. The actuarial relapse-free survival for patients treated by local versus extended field radiotherapy significantly favors the extended field technique although the rates of relapse after complete remission has been achieved appear similar. Immunosuppression was present in 12 patients prior to the diagnosis of Kaposi's sarcoma; these patients had a similar response rate to radiation therapy to those who were not known to be immunosuppressed. A rationale for management, and radiation technique and dose are discussed. It is concluded that radiotherapy is an effective treatment for most forms of Kaposi's sarcoma.

External irradiation for squamous cell carcinoma of the nasal vestibule.

A retrospective analysis of 56 patients who underwent primary external irradiation for squamous cell carcinoma of the nasal vestibule between 1958 and 1983 is presented. The overall 5 year actuarial survival and cause specific survival rates were 64 and 87%, respectively. The 5-year local relapse-free rate after primary irradiation was 80%. Prognostic factors which lowered the local control rate after irradiation included a primary tumor size of 2 cm or more, or involvement of the skin of the ala nasi, columella, lip, cartilage, or bone. Local control was improved in patients who received a tumor dose equivalent to, or greater than, 5500 cGy/25 fractions/5 weeks. Only two patients in whom the primary tumor was controlled developed regional nodal metastases, and elective regional nodal irradiation is not recommended. Four patients (9%) developed significant late morbidity after irradiation. External irradiation is effective treatment for squamous cell carcinoma of the nasal vestibule, and produces high local control and cure rates and good cosmetic results.

Chordoma: the results of megavoltage radiation therapy.

Twenty-four patients with chordoma who received one or more courses of megavoltage radiation therapy following biopsy or incomplete resection were reviewed. The uncorrected survival rate at five years was 62%, and at 10 years was 28%, but most patients had clinically detectable residual chordoma present at the time of death or last follow-up. The duration of symptomatic improvement following irradiation ranged from a few months to 18 years, median 3.5 years. Detailed dose-time and symptomatic response data for 56 patients from this series and from the literature who were treated by conventional daily fractionated megavoltage irradiation show no convincing evidence that symptomatic relief is more likely after high doses than after total doses of only 4000 to 5500 cGy. Patients are rarely cured of chordoma by partial tumor resection and conventional radiation. Four patients received multiple fractions of 100 cGy each day either as retreatment for recurrence, or as initial treatment. Symptomatic responses, and decreases in the size of tumor masses, were seen following total doses ranging from 2000 cGy/20 fractions/5 days/4 X 3 hourly fractions each day to 4000 cGy/40 fractions/12 days/4 X 3 hourly fractions each day. The short duration of follow-up in these patients prevents comparison with conventional fractionation. However, this technique presents one possible new approach for the treatment of chordoma.

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.