Relationship between testosterone, estradiol and circulating PCSK9: Cross-sectional and interventional studies in humans.

BACKGROUND: Circulating PCSK9 levels are higher in women than men, in postmenopausal than premenopausal women, and in pregnant than non-pregnant women, suggesting that sex hormones may be related to PCSK9 levels. We have examined the relationship between serum estradiol (E2) and testosterone (T) and PCSK9, and the impact of E2 replacement therapy in women and T replacement and ablation therapy in men on circulating PCSK9. METHODS: We conducted a cross-sectional study to examine the correlation between serum T (in males) and E2 (in females) and serum PCSK9. We also conducted interventional studies to examine the effect of hormonal therapy on serum PCSK9 levels. RESULTS: In men, (1) serum T does not correlate with circulating PCSK9 or with LDLC in the basal state, (2) T replacement therapy does not have any effect on circulating PCSK9, and (3) T ablation therapy has mixed results. In women, (1) E2 correlates inversely with circulating PCSK9 and directly with serum LDLC, but (2) E2 replacement therapy does not have any effect on circulating PCSK9. CONCLUSIONS: We demonstrate differences between men and women in the relationship of their major sex hormones with circulating PCSK9. In men, circulating PCSK9 is not related to or affected by T except for a possible effect during T ablation therapy. In women, E2 is inversely related to circulating PCSK9 but the lack of effect of E2 therapy on circulating PCSK9 suggests that the E2-related differences in PCSK9 levels may be the result of differences in receptor-mediated PCSK9 clearance through E2-induced changes rather than production of PCSK9. The studies were registered with ClinicalTrials.gov NCT00848276.

Spontaneous regression of metastatic melanoma after inoculation with tetanus-diphtheria-pertussis vaccine.

Spontaneous regression of metastatic melanoma is an exceedingly rare event, with only 76 well-documented cases in the literature since 1866. Here, we present the case of a patient who developed metastatic melanoma despite interferon therapy and who then achieved spontaneous regression shortly after a reaction to tetanus-diphtheria-pertussis vaccination. A common theme among these cases is the development of febrile illness before remission of the malignant disease. A brief overview of proposed mechanisms for these miraculous recoveries is presented, including a highlight on the potential role of the herv-k-mel viral marker, a nona- or decapeptide that appears in most melanomas, with homologies to peptides in pathogenic microorganisms.

Effects of radiation and total androgen blockade on serum hemoglobin, testosterone, and erythropoietin in patients with localized prostate cancer.

OBJECTIVE: The objective of the present study was to evaluate the incidence, time of onset, and extent of hemoglobin, testosterone, and erythropoietin changes in patients with localized prostate cancer receiving either radiation alone or radiation combined with total androgen blockade (tab). METHODS: The study enrolled 35 patients (median age: 69 years) with clinically localized prostate cancer who received 3-dimensional conformal radiation with or without tab. Patients were generally treated with radiation alone (group 1), radiation plus short-term (≤6 months) tab (group 2), or radiation plus long-term (≥2 years) tab (group 3). Serum hemoglobin, testosterone, and erythropoietin in these patients were prospectively evaluated. RESULTS: The mean baseline serum hemoglobin for group 1 (n = 20), group 2 (n = 6), and group 3 (n = 9) was 149 g/L, 153 g/L, and 143 g/L respectively. We observed no significant decline in serum hemoglobin, testosterone, or erythropoietin among patients treated with radiotherapy alone. A significant drop in serum testosterone was noted in the group 2 and 3 patients within 1 month (p < 0.001), reaching a plateau at approximately 6 months. That change was followed by a significant decline (p < 0.001) in serum hemoglobin at 3-6 months (137 g/L in group 2 and 129 g/L in group 3). We observed a small but statistically significant increase in serum erythropoietin (p < 0.001) of 8 U/L in group 2 and 4 U/L in group 3 after 6 months of tab. No immediate recovery in serum hemoglobin, testosterone, or erythropoietin was observed upon completion of tab. CONCLUSIONS: Although conformal radiotherapy alone for localized prostate cancer had no effect on serum hemoglobin, testosterone, or erythropoietin, tab led to a significant decline in testosterone, which was followed by decline in hemoglobin that was not a result of a deficiency of erythropoietin.

Laryngeal cancer treatment and survival differences across regional cancer centres in Ontario, Canada.

AIMS: We conducted a population-based study of practice patterns and outcome across the regional cancer centres providing care to patients with laryngeal cancer in the Province of Ontario, Canada. MATERIALS AND METHODS: : This was a retrospective cohort study of 1547 patients with cancers of the glottic or supraglottic larynx diagnosed between 1982 and 1995. Data were collected via chart review, including: patient and disease characteristics, treatment, waiting times and treatment volumes. Vital status was obtained from the Ontario Cancer Registry. Variations across the nine regional cancer centres are described and their effect on outcome explored. All analyses were stratified by stage I and II separately from stage III and IV. RESULTS: Treatments differed across centres (P<0.0001); for instance, in the stage I and II group, use of a daily dose of >2.54Gy varied from 0 to 87.6% and in the stage III and IV group, total laryngectomy rates varied from a low of 6% to a high of 53%. The percentage of patients waiting more than 6 weeks from diagnosis to first treatment varied from 17 to 49% (P<0.0001). Multivariate analysis revealed cause-specific survival differences that were not explained by control for case mix, treatment or waiting times. Differences ranged from an 82% risk reduction in one centre compared with the reference (stage I and II group, P=0.008) to a 153% increase in risk (stage III and IV group, P=0.02). Centre case volumes were not associated with cause-specific survival. CONCLUSIONS: This study quantifies the degree of variation that can occur in the treatment and outcome of people with cancer. We cannot properly assess whether care delivery is of high quality until we have a better understanding of the factors that drive such variations.

Contemporary management of stage I testicular seminoma: a survey of Canadian radiation oncologists.

Recently published studies clearly indicate that there are now several acceptable options for managing stage i testicular seminoma patients after orchiectomy. We therefore decided to survey Canadian radiation oncologists to determine how they currently manage such patients and to compare the results with previous surveys. Our results demonstrate that adjuvant single-agent chemotherapy is being considered as an option by an increasing proportion of radiation oncologists (although it is not considered the preferred option), the routine use of radiotherapy is declining, and surveillance is becoming increasingly popular and is recommended most often.

The preferred treatment for stage I seminoma: a survey of Canadian radiation oncologists.

AIMS: To evaluate the preferences of radiation oncologists for managing stage I seminoma. MATERIALS AND METHODS: An electronic survey evaluating the management of stage I seminoma patients was sent to Canadian radiation oncologists to determine their treatment recommendations and preferences. RESULTS: The survey completion rate was 74% among eligible respondents (78/105). Most (56%) felt that surveillance was the preferred treatment for patients, whereas 31% thought that adjuvant radiotherapy was best, 1% chose adjuvant chemotherapy as being the preferred option and 12% were unsure. Most would choose the same treatment for themselves if they were diagnosed with stage I seminoma. A previously published survey found that most respondents considered radiotherapy as the best option. CONCLUSIONS: Most Canadian radiation oncologists now favour surveillance for most stage I seminoma patients.

Explaining socioeconomic status effects in laryngeal cancer.

INTRODUCTION: People with lower socioeconomic status (SES) experience shorter survival times after a cancer diagnosis for many disease sites. We determined whether area-level SES was associated with the outcomes: cause-specific survival and local-regional failure in laryngeal cancer in Ontario, Canada. When we found an association we sought explanations that might be related to access to care including age, sex, rural residence, tumor stage, lymph node status, use of diagnostic imaging, treatment type, percentage of prescribed radiotherapy delivered, number of radiotherapy interruption days, treatment waiting time, and treating cancer center. MATERIALS AND METHODS: The study population consisted of 661 glottic and 495 supraglottic stage-stratified randomly-sampled patients identified using the Ontario Cancer Registry. Area-level SES quintiles were assigned using adjusted median household income from the Canadian Census. Other data were collected from patient charts. Explanations for SES effects were determined by measuring whether the effect moved toward the null value by at least 10% when an access indicator was added to a the model. RESULTS: Socioeconomic status was not related to either outcome for those with supraglottic cancer, but an association was present in glottic cancer. With the highest socioeconomic status quintile as the referent group, the relative risks for patients in the lowest socioeconomic quintile were 2.75 (95% CI 1.48, 5.12) for cause-specific survival and 1.90 (95% CI 1.24, 2.93) for local-regional failure. Disease stage as measured by T-category explained between 3% and 23% of these socioeconomic effects. None of the other access indicators met our 10% change criterion. CONCLUSION: We question why people in lower socioeconomic quintiles were not diagnosed earlier in the disease progression. Having ruled out several variables that may be related to access to care, additional biologic and social variables should be examined to further understand socioeconomic status effects.

Clinical use of a commercial Monte Carlo treatment planning system for electron beams.

In 2002 we fully implemented clinically a commercial Monte Carlo based treatment planning system for electron beams. The software, developed by MDS Nordion (presently Nucletron), is based on Kawrakow's VMC++ algorithm. The Monte Carlo module is integrated with our Theraplan Plustrade mark treatment planning system. An extensive commissioning process preceded clinical implementation of this software. Using a single virtual 'machine' for each electron beam energy, we can now calculate very accurately the dose distributions and the number of MU for any arbitrary field shape and SSD. This new treatment planning capability has significantly impacted our clinical practice. Since we are more confident of the actual dose delivered to a patient, we now calculate accurate three-dimensional (3D) dose distributions for a greater variety of techniques and anatomical sites than we have in the past. We use the Monte Carlo module to calculate dose for head and neck, breast, chest wall and abdominal treatments with electron beams applied either solo or in conjunction with photons. In some cases patient treatment decisions have been changed, as compared to how such patients would have been treated in the past. In this paper, we present the planning procedure and some clinical examples.

Radiotherapy patterns of practice: T1N0 glottic cancer in Ontario, Canada.

AIMS: To describe the variation in the delivery of radiation therapy to patients with T1N0 glottic cancer who were diagnosed in Ontario, Canada, between 1982 and 1995. MATERIALS AND METHODS: The patient population consisted of a random sample of 461 patients treated with curative intent from the nine cancer centres that administer radiation therapy in the province. Abstracted variables included prescribed dose (Gy) and fractionation (f), beam energy and arrangement, set-up, field size, beam modifiers, positioning and treatment interruptions. RESULTS: Thirteen prescribed dose-fractionation schemes (> or = four cases each) were identified, including 50.0-53.0 Gy/20 f (54.5%), 55.0-61.0 Gy/25 f (30.3%), and 60.0-66.0 Gy/30-33 f (7.7%). All regimens used one fraction per day, 5 days per week. An isocentric set-up was used (94.3%), with megavoltage (MV) beam energies of Cobalt-60 (87.9%), 6 MV (6.1%) and 4 MV (6.1%). A lateral parallel-opposed pair of beams was the predominant technique (76.4%) versus an anterior oblique pair (17.2%) or angle-down pair (caudally directed fields to achieve shoulder clearance, 5.7%). Wedging (96.3%) and bolus (11.8%) were used as beam-modifying devices. Predominant field-width dimensions were 5.0-6.0 cm (43.4%) and 6.5-7.0 cm (43.1%), and field length dimensions were 5.0-6.0 cm (49.5%) and 6.5-7.0 cm (35.0%). Head, neck or chin immobilisation was used in 86.9% of the cases, with 94.6% of these being custom-made. We found that radiotherapy practice was stable over time, except for a trend of increasing field size and increasing use of immobilisation. In contrast, we found practice variations among the province's cancer centres. On the basis of our findings, we defined a predominant technical practice consisting of Cobalt-60 (reflecting machine availability during the period of the study), an isocentric set-up, a lateral parallel-opposed pair technique with wedging, and supine-head neutral positioning with custom immobilisation. Forty-two per cent of the cases had one or more components of treatment that differed from this definition. CONCLUSIONS: Description of practice variation can provoke discussion about unrecognised differences in practice policies, perhaps identifying the need for better evidence, treatment guidelines, or both.

Treatment planning aids in prostate cancer: friend or foe?

BACKGROUND: Rectal barium is commonly used as a treatment planning aid for prostate cancer to delineate the anterior rectal wall. Previous research at the Ottawa Regional Cancer Centre demonstrated that retrograde urethrography results in a systematic shift of the prostate. We postulated that rectal barium could also cause prostate motion. PURPOSE: The study was designed to evaluate the effects of rectal barium on prostate position. METHODS AND MATERIALS: Thirty patients with cT1-T3 prostate cancer were evaluated. Three fiducial markers were placed in the prostate. During simulation, baseline posterior-anterior and lateral films were taken. Repeat films were taken after rectal barium opacification. The prostate position (identified by the fiducials) relative to bony landmarks was compared before and after rectal barium. Films were analyzed using PIPsPro software. RESULTS: The rectal barium procedure resulted in a significant displacement of the prostate in the anterior and superior direction. The mean displacement of the prostate measured on the lateral films was 3.8 mm (SD: 4.4 mm) in the superior direction and 3.0 mm (SD: 3.1) in the anterior direction. CONCLUSIONS: Rectal barium opacification results in a systematic shift of the prostate. This error could result in a geographic miss of the target; therefore, alternate methods of normal tissue definition should be used.

The role of computed tomography in the T classification of laryngeal carcinoma.

BACKGROUND: The objectives of this study were 1) to describe patterns of use of computed tomography (CT) in laryngeal carcinoma, and 2) to characterize the contribution of CT to the T classification of laryngeal carcinoma. METHODS: The study population comprised 1195 patients with laryngeal carcinoma diagnosed from 1982 through 1995 chosen randomly from the Ontario provincial cancer registry. A chart review was conducted to obtain data on each case. Patient-related, tumor-related, and health-system-related factors were analyzed to identify factors associated with the use of CT. Descriptions of clinical exams and CT reports were reviewed to see how CT information modified T classification. Actuarial local control and cause specific survival curves were plotted by clinical T classification without and with CT to evaluate stage migration. The percentage of the variance in outcome explained by T classification in a Cox analysis was used to evaluate whether the prognostic accuracy of T classification was improved with the use of information from CT. RESULTS: Patients with glottic (20.1%) and supraglottic (41.7%) carcinoma underwent CT. The use of CT increased over time in glottic and supraglottic carcinoma combined from 17.2% in 1982-5 to 33.9% in 1991-5. Computed tomography was used less often in older patients with a 16% (95% confidence interval, 5-27%) decrease in the odds of having CT with each 10-year age increment. Computed tomography use varied considerably across the cancer center regions in Ontario. Computed tomography altered the T classification in 20.2% of those patients who had CT, with most being "upstages." Stage migration due to CT was demonstrated. Using information from CT in the assignment of T classification for 27.8% of this study population did not make a significant contribution to the ability of T classification to predict outcome over the entire group. CONCLUSIONS: There is large variation in the use of CT among different age groups and regions. The ability to compare outcomes by stage across geographic areas is compromised when the use of CT varies.

Glottic cancer in Ontario, Canada and the SEER areas of the United States. Do different management philosophies produce different outcome profiles?

We compared the management and outcome of glottic cancer in Ontario, Canada to that in the Surveillance, Epidemiology and End Results (SEER) Program areas in the United States to determine whether the greater use of primary radiotherapy with surgery reserved for salvage in Ontario was associated with similar survival and better larynx retention rates than the U.S. approach where primary surgery is used more often. Electronic, clinical and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Initial treatment and survival in patients diagnosed in the SEER areas from 1988 through 1994 were compared to patients from Ontario diagnosed from 1982 through 1995. Actuarial laryngectomy rates were compared for patients over 65 at diagnosis in the two regions. Analyses were conducted over all cases and stratified by disease stage. In localized disease (T1 or T2), conservative treatment was the most common initial treatment in both regions, although total laryngectomy was used more often in SEER than Ontario (6.2% vs. 0.2%, respectively, P <.001). In advanced disease (T3 or T4), total laryngectomy was more commonly used as initial treatment in SEER (62.9% vs. 21.0% in Ontario, P < or =.001). Over all cases, the relative survival rate was 80% in Ontario at 5 years compared to 78% in SEER (P =.33). In localized disease, the relative survival rates were 4 to 5% higher in Ontario from the second year on, while in advanced disease 2 to 3% higher rates in SEER did not approach statistical significance. Actuarial laryngectomy rates at 3 years differed between the two regions, with a 4% higher rate in SEER (P =.01). In localized disease, 12.6% of Ontario patients had a laryngectomy by 3 years postdiagnosis compared to 17.9% in SEER (P =.05). In advanced disease, the rates were 63.3% and 79.2%, respectively (P =.07). There are large differences in the management of glottic cancer between the SEER areas of the U.S. and Ontario and no evidence that a policy emphasizing radiotherapy with surgery reserved for salvage is associated with worse survival. Ultimate laryngectomy rates are lower in Ontario for localized disease and may be lower for advanced disease. Conservation treatment should be used for localized disease while the treatment decision in advanced disease may be especially sensitive to patient values for voice retention versus initial cure.

Comorbid survival among elderly male participants of the Canada health survey: relevance to prostate cancer screening and treatment.

This study assessed the survival of a nationally representative sample of older Canadian men, taking into account common comorbid conditions. Mortality follow-up between 1978 and 1989 was conducted for male participants of the Canada Health Survey who were at least 60 years of age at baseline. The proportional hazards model and life table methods were used to examine survival by comorbidity status. Comorbid conditions examined included history of stroke and/or heart disease, high blood pressure, chronic bronchitis or emphysema, diabetes and smoking status, but excluded cancer because of small numbers. For those subjects aged 80 and older, comorbidity was not a significant predictor of survival. A large portion of men between the ages of 60 and 79, even those with pre-existing comorbid conditions, survived at least 10 years after interview. In a clinical setting, more detailed information on comorbid conditions can be obtained to better estimate long-term survival. Notwithstanding, our findings may have implications for the administration of population-based health interventions (e.g. the use of prostate-specific antigen [PSA] blood tests for the early detection of prostate cancer). In particular, our results suggest that there may be little benefit in restricting access to PSA screening based on survival probability in men under age 80.

Is prostate specific antigen density an important prognostic indicator for patients with prostate cancer treated with external beam therapy?

The purpose of this study was to determine if prostate specific antigen density (PSAD) is a predictor of outcome following external beam radiotherapy for prostate cancer, and to compare it with other prognostic factors. Between January 1990 and December 1993, 205 patients with T1-T3 adenocarcinoma of the prostate received a radical course of external beam irradiation, with no prior or adjuvant hormonal therapy. All patients had pre- and post-treatment serum prostate specific antigen (PSA) evaluation. They were followed up for at least 24 months. PSAD was defined as the ratio of pre-treatment serum PSA to the prostate volume, as determined from CT treatment planning scans. Prostate volumes were calculated using the prostate ellipse formula. Median PSA density was 0.37, with a range 0.01-6.7. Biochemical failure was defined as three consecutive rises in serum PSA, regardless of the magnitude of elevation. 4-year biochemical disease-free survival (BDFS) for patients with PSAD < or = 0.3 was 60%, compared with 22% for patients with PSAD > 0.3 (p = < 0.001). In a multivariate analysis, pre-treatment PSA (p = < 0.001), Gleason score (p = 0.002), and stage (p = 0.03) were independent predictors of BDFS, while PSAD was not an important prognosticator (p = 0.62). Pre-treatment serum PSA is the most important prognosticator of BDFS, following external beam radiotherapy, for patients with prostate cancer. PSA density did not predict treatment outcome.

The relationship between biochemical failure and time to nadir in patients treated with external beam therapy for T1-T3 prostate carcinoma.

PURPOSE AND BACKGROUND: To determine a prostatic-specific antigen (PSA) nadir value and time to nadir that predict a high probability of freedom from biochemical failure in men treated with external beam therapy for prostate cancer. MATERIALS AND METHODS: Between January 1990 and March 1994, 228 men with T1-T3 adenocarcinoma of the prostate received a radical course of external beam irradiation with no prior or adjuvant hormonal therapy. All men had pre- and post-treatment serum PSA evaluations, and were followed up for at least 24 months, to ensure PSA nadir was reached. Biochemical failure was defined as three successive post-treatment rises in serum PSA, regardless of the magnitude of elevation. RESULTS: Overall, 4-year biochemical disease-free survival (BDFS) was 42%. PSA nadir was predictive of subsequent BDFS. For those whose serum PSA nadir was < or =1 ng/ml, 4-year BDFS was 70%, versus 12% for those with serum PSA nadir > 1 ng/ml (P = < 0.001). The 4-year BDFS for patients with time to nadir < or =1 year, was 28%, versus 58% for those with time to nadir > 1 year (P < 0.001). For patients with PSA nadir < or =1 ng/ml, 4-year BDFS was 75% for those with time to nadir > 1 year, versus 61% for those with time to nadir < or =1 year (P < 0.021). In multivariate analysis, PSA nadir(< or =1 ng/ml versus >1 ng/ml, and time to nadir (< or =1 year versus > year) were independent predictors of BDFS alone with pre-treatment PSA and Gleason score. CONCLUSION: Only those who achieved PSA nadir < or =1 ng/ml following external beam therapy have a favourable chance of lasting biochemical disease control, while those with nadir > 1 ng/ml have a high subsequent failure rate. The prognosis is better in patients with late time to nadir. In addition to PSA nadir, time to nadir, pretreatment PSA, and Gleason score were of independent prognostic significance.

[Treatment of cancer of the bladder in elderly patients with an intra-arterial chemotherapy and radiotherapy combination: 10-year experience]. / Traitement du cancer de la vessie chez les patients âgés par association de chimiothérapie intra-artérielle et de radiothérapie: 10 ans d'expérience.

PURPOSE: Analysis of the results obtained in elderly (75 years and older) included a phase II trial combining intra-arterial cisplatin and concurrent radiation into invasive bladder cancer. PATIENTS AND METHODS: Thirty-five patients (28 males and 7 females) were accrued from 1985 to 1996. There were 1 Ta, 4 T2, 11 T3A, 12 T3B, 3 T4A, and 4 T4B patients. Nine had unilateral hydronephrosis and two bilateral hydronephrosis. There were 28 transurethral resections which were incomplete in 23 patients. Intra-arterial cisplatin was given as 2-4 hours infusion (60-90 mg/m2) split through both internal iliac arteries on day 1, 14, 21, and 42. Irradiation to the pelvis was started on day 14 and consisted of 40 Gy/20 fractions followed by a boost of 20 Gy/10 fractions to the tumor with margins of 2 cm. RESULTS: Thirty (86%) completed fully the protocol. One patient died from sepsis secondary to the treatment. The tumor response was evaluable in 29 patients and complete response was observed for 27 of them. Five of these 27 patients had an isolated bladder relapse which was salvaged by cystectomy in two patients. There were 11 deaths from bladder cancer (31% of the patients): 9 from distant metastase, one from local failure, and one from treatment. CONCLUSION: This combined modality yields excellent results with high complete response rate and good tolerance. This approach may therefore be particularly appropriate for the elderly.

PROMACE-MOPP and intrathecal chemotherapy for CNS lymphomas.

UNLABELLED: We conducted a Phase II study of PROMACE-MOPP and intrathecal (IT) therapy followed by cranial radiation in 7 patients (4 male, 3 females) with diffuse large cell lymphomas (including one T cell) involving the central nervous system (CNS). Median age was 47 years (range, 25-78). Median performance status was 2 (range, 2 to 3). Two patients had positive CSF cytology. No patients had prior chemotherapy or radiotherapy. Treatment consisted of PROMACE (cyclophosphamide 650 mg/m2, etoposide 120 mg/m2 days 1 and 8, methotrexate (MTX) 1.5 g/m2 and folinic acid 50 mg/m2 (x 5) day 15, and prednisone 60 mg/m2 days 1-14) x 3-4 courses. MOPP consisted of mustargen 6 mg/m2 and vincristine 1.4 mg/m2 days 1 and 8, procarbazine 100 mg/m2 and prednisone 40 mg/m2 po days 1-14 x 3-4 courses. IT drugs were MTX 20 mg and hydrocortisone 20 mg day 1 and cytosine arabinoside 100 mg day 8, courses 2 to 6, or more frequently if CSF cytology was positive. Following MOPP, 4000 cGy whole brain radiation (XRT) and 2000 cGy boost was given. Response was evaluated before XRT. Two patients declined XRT, 3 declined MOPP and 2 declined IT drugs. Two patients had extracerebral disease and 5 were primary CNS lymphomas. Response after PROMACE was CR: 3 patients; PR 2: stable 1. One patient, with extracerebral disease, experienced PR in the abdomen and CR by CT scan in the brain, but had persistent positive CSF cytology. This patient died from pneumocystis pneumonia 10 weeks after her last CSF cytology and 17 weeks after her diagnosis. After PROMACE +/- MOPP 6 patients experienced CR's. Median (range) survival was 100 (17-334) weeks, with 1 patient lost to follow up at 32 weeks. Toxicity included febrile neutropenia; 6 patients; pneumocystis pneumonia: 1 (fatal); thrombocytopenia; 5; stomatitis: 3; diarrhea; 2; nausea; 3. CONCLUSION: This regimen is active in the treatment of CNS lymphomas, although toxicity is substantial.

The role of palliative radiotherapy in advanced head and neck cancer.

The role of radiotherapy in the palliation of patients with advanced cancer of the head and neck is not clear. Several distinctive characteristics of advanced head and neck cancer contribute to the complexities in the choice of appropriate palliative management strategies. Palliative treatment may be the appropriate management for a proportion of patients with advanced disease, but the current stage groupings of head and neck cancer are not sufficient for use in the reliable identification of such a patient group. Controversy arises because of the difficulties in distinguishing patients who should be offered conventional treatment with curative intent from those appropriate for treatment with palliative intent. A structured review of the cancer and quality of life literature identified 298 references pertaining to palliative radiotherapy in head and neck cancer, 26 of which met the criteria for inclusion in this review. An expert panel discussed the literature, and concluded that insufficient information precluded estimations of the frequency, degree of, or duration of symptomatic relief that radiation offered to those patients not cured of their disease. Moreover, the currently available literature does not address the toxicity or appropriate dose and fractionation of palliative radiotherapy in this setting. Further studies are necessary to evaluate clinical endpoints appropriate to the use of radiotherapy in the palliative management of patients with advanced head and neck cancer. Studies are also needed to refine the current clinical classification of patients, allowing the identification of patients suitable for palliative management.

Asymmetric arc technique for posterior pharyngeal wall and retropharyngeal space tumors.

PURPOSE: Tumors of the posterior pharyngeal wall and nasopharyngeal cancer with retropharyngeal extension can partly encircle the cervical vertebrae. Treating the patient within spinal cord tolerance can cause a geographic miss. A simple technique has been developed to avoid this problem. METHODS AND MATERIALS: The standard fields for posterior pharyngeal wall and nasopharyngeal tumors are used up to 36-40 Gy. A planning computed tomography (CT) scan is taken during the second or third week of treatment with the patient fitted in a new shell ensuring that the cord is straight and parallel to the treatment couch. The asymmetric arc technique consists of two posterior arcs with closure of one jaw beyond the central axis. Each arc delivers the total dose to each ipsilateral side, while the median region of the U-shaped volume is treated by the summation of both arcs. RESULTS: We have treated 10 patients using asymmetric arcs in the last 3 years. This technique proved to be a versatile way of treating targets wrapped around the spine. The technique allows better individualization for target volume irregularities than the partial rotation with a central bar.

Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer.

PURPOSE: To determine whether the addition of infusional fluorouracil (I-FU) to standard radiotherapy improves survival at acceptable toxicity in patients with locally advanced squamous cell head and neck cancer (SCHNC). PATIENTS AND METHODS: Consenting patients with an Eastern Cooperative Oncology Group (ECOG) performance status < or = 2; with stage III or IV SCHNC of the oral cavity, oropharynx, hypopharynx, or larynx; and who were recommended for radiotherapy with curative intent received 66 Gy of radiation therapy delivered in 2-Gy fractions once daily 5 days per week for 6 1/2 weeks. Those in the experimental arm received I-FU 1.2 g/m2/d, as a 72-hour infusion in the first and third weeks of radiation. Saline infusions were used in the placebo arm. RESULTS: One hundred seventy-five patients were randomized (88 to I-FU and 87 to placebo), and the treatment arms were well balanced. The complete response rate was 68% for I-FU and 56% for placebo (P = .04). The overall median survival duration was 33 months for I-FU and 25 months for placebo (P = .08). Progression-free survival also favored I-FU (P = .06). Toxicity was greater in I-FU patients, but did not interfere with the scheduled delivery or completion of radiation. CONCLUSION: The addition of I-FU to standard radiation in SCHNC improved the complete response rate and was associated with beneficial trends in progression-free and overall survival compared with radiation alone. I-FU patients also experienced greater morbidity, but this did not compromise delivery of radiotherapy.