Descriptive Analysis of First-Line Non-Small Cell Lung Cancer Treatment with Pembrolizumab in Tumors Expressing PD-L1 ≥ 50% in Patients Treated in Quebec's University Teaching Hospitals (DALP-First Study).

Since July 2017, pembrolizumab has been approved as a first-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients with a PD-L1 score ≥ 50% in Quebec. Study objectives were to describe and assess the real-world use of pembrolizumab; report progression-free survival (PFS), overall survival (OS), and immune-related adverse events (IRAEs); and compare outcomes between a fixed dose (FD) and a weight-based capped dose (WCD). Medical records of patients treated in one of Quebec's four adult university teaching hospitals who received pembrolizumab between 1 November 2017 and 31 October 2019 were reviewed and followed until 29 February 2020. Two hundred and seventy-nine patients were included. The median real-world PFS and OS were 9.4 (95% CI, 6.6 to 11.2) and 17.3 months (95% CI, 12.9 to not reached), respectively. IRAEs causing delays or treatment interruptions were seen in 34.4% of patients. Initiating treatment with a FD (49 patients) or using a WCD (230 patients) does not appear to affect PFS, OS, or the occurrence of IRAEs. The use of a WCD strategy allowed approximately CAD 5.8 million in savings during the course of our study. These findings support the effectiveness and safety of pembrolizumab in a real-world setting. The use of a WCD does not appear to have a negative impact on patient outcomes.

Role of Serum Lymphocyte-derived Biomarkers in Nonmetastatic Muscle-invasive Bladder Cancer Patients Treated with Trimodal Therapy.

BACKGROUND: The role of serum lymphocyte-based biomarkers, such as the neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR), and platelet-to-lymphocyte (PLR) ratios, was previously studied in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy but remains underexplored in patients treated with trimodal therapy (TMT). OBJECTIVE: To analyze the impact of serum lymphocyte-based biomarkers on main oncological outcomes after TMT for MIBC. DESIGN SETTING AND PARTICIPANTS: A retrospective study, including 176 patients treated with TMT for nonmetastatic MIBC (cT2-4/cN0-2) between 2001 and 2017 at a tertiary academic center, was conducted. INTERVENTION: TMT, consisting of initial maximal transurethral resection of the bladder tumor, followed by radiotherapy with concurrent chemotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinicopathological characteristics, serum laboratory tests, and imaging reports were collected. NLR, LMR, and PLR were calculated before and at the end of TMT. Dynamic patterns of NLR, LMR, and PLR during TMT were studied. Multivariable regression models were performed to estimate the effect of these biomarkers on complete response (CR) to TMT and survival. RESULTS AND LIMITATIONS: The median age was 75 yr (interquartile range 66-82). Staging was cT2 in 156 (89%) and cN0 in 159 (90%) patients. A pretreatment NLR (pre-NLR) of ≥4.0 was independently associated with lower CR rates (odds ratio 0.32; p = 0.013). In addition, a pre-NLR of ≥4.0 was associated with worse cancer-specific survival (hazard ratio [HR] 1.88; p = 0.032) and overall survival (OS; HR 1.61; p = 0.033) together with other factors such as hydronephrosis, Eastern Cooperative Oncology Group performance status, and cT stage 3-4a. When both pre- and post-treatment variables were considered, an increase in NLR beyond 75% during TMT (HR 1.63; p = 0.035) was associated with worse OS. This study was limited by its retrospective design. CONCLUSIONS: A high pre-NLR value was independently associated with lower rates of CR and worse survival in MIBC patients undergoing TMT. Prospective validation is needed to implement NLR into clinical practice. PATIENT SUMMARY: In this study, we reported the oncological outcomes of patients with muscle-invasive bladder cancer treated with trimodal therapy. We found that the neutrophil-to-lymphocyte ratio, a cheap and available blood-derived biomarker, was associated with response to trimodal therapy and survival outcomes.

Phase 1 Trial of Atezolizumab Plus Trimodal Therapy in Patients With Localized Muscle-Invasive Bladder Cancer.

PURPOSE: Immune checkpoint programmed death-ligand 1 inhibitor therapy has shown response in metastatic muscle invasive bladder cancer (MIBC). We evaluated the safety and tolerability of atezolizumab (anti-programmed death-ligand 1) in combination with trimodal therapy in patients with localized MIBC. METHODS AND MATERIALS: A prospective nonrandomized phase 1 study using a 3 + 3 design was conducted in patients with localized MIBC (T2-T4a N0M0) treated on a bladder preservation program. After transurethral resection of bladder tumor, patients received concurrent radiation therapy at a fixed dose of 50 Gy in 20 fractions, gemcitabine (100 mg/m2, intravenously once weekly for 4 weeks) and atezolizumab (1200 mg intravenously every 3 weeks for 16 cycles). The primary endpoint was safety/toxicity profile. RESULTS: Between May 2018 and March 2019, 8 patients (6 male and 2 female) were enrolled. The first 5 patients received atezolizumab at 1200 mg, 3 of whom developed grade 3 side effects (2 of them dose-limiting toxicity). Atezolizumab dose was reduced to 840 mg for 3 additional patients. The study was terminated due to the presence of 3 grade 3 adverse events (2 of which were dose-limiting toxicity) despite the reduced atezolizumab dose. Gastrointestinal events were the main toxicity. No grade 4 to 5 adverse effects were observed. CONCLUSIONS: Concurrent administration of atezolizumab with concomitant hypofractionated radiation therapy and gemcitabine appears to be associated with unacceptable gastrointestinal toxicity. Although the numbers studied are small, our results suggest considerable caution with its concurrent use with trimodal therapy for MIBC.

A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902.

PURPOSE: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS). METHODS AND MATERIALS: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥ 7 or clinical stage ≥ T2 and GS ≥ 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05. RESULTS: A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61). CONCLUSIONS: NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for the feasibility of clinical trial accrual and tolerability using CT for PCa.

Adjuvant treatment for endometrial cancer: literature review and recommendations by the Comité de l'évolution des pratiques en oncologie (CEPO).

OBJECTIVE: Despite the very good prognosis of endometrial cancer, a number of patients with localized disease relapse following surgery. Therefore, various adjuvant therapeutic approaches have been studied. The objective of this review is to evaluate the efficacy and safety of neoadjuvant and adjuvant therapies in patients with resectable endometrial cancer and to develop evidence-based recommendations. METHODS: A review of the scientific literature published between January 1990 and June 2012 was performed. The search was limited to published phase III clinical trials and meta-analyses evaluating the efficacy of neoadjuvant or adjuvant therapies in patients with endometrial carcinoma or carcinosarcoma. A total of 23 studies and five meta-analyses were identified. RESULTS: The selected literature showed that in patients with a low risk of recurrence, post-surgical observation is safe and recommended in most cases. There are several therapeutic modalities available for treatment of endometrial cancers with higher risk of recurrence, including vaginal brachytherapy, external beam radiotherapy, chemotherapy, or a combination of these. CONCLUSIONS: Considering the evidence available to date, the CEPO recommends the following: (1)post-surgical observation for most patients with a low recurrence risk; (2)adjuvant vaginal brachytherapy for patients with an intermediate recurrence risk; (3)adjuvant pelvic radiotherapy with or without vaginal brachytherapy for patients with a high recurrence risk; addition of adjuvant chemotherapy may be considered as an option for selected patients (excellent functional status, no significant co-morbidities, poor prognostic factors); (4)adjuvant chemotherapy and pelvic radiotherapy with or without brachytherapy and para-aortic irradiation for patients with advanced disease;

Response to chemotherapy in metastatic colorectal cancer after exposure to oxaliplatin in the adjuvant setting.

AIM: Oxaliplatin with 5-fluorouracil (5-FU) and leucovorin (FOLFOX and FLOX) or capecitabine (XELOX) is the standard adjuvant treatment for colonic cancer. In metastatic disease, 5-FU/leucovorin/irinotecan (FOLFIRI) and FOLFOX are equivalent in respect to response rates, progression-free and overall survival. Little data are available to compare their efficacy after exposure to oxaliplatin-containing adjuvant chemotherapy. PATIENTS AND METHODS: We carried out a retrospective study of patients who underwent surgery and FOLFOX adjuvant chemotherapy, followed by FOLFIRI or FOLFOX for metastatic disease. Exclusion criteria were: metastatic disease at presentation and no oxaliplatin in adjuvant chemotherapy. The end-point was the overall response rate (ORR) to first-line chemotherapy for metastatic disease after three months, as assessed by computed tomography (CT). RESULTS: A total of 205 patients received FOLFOX as adjuvant treatment for colorectal adenocarcinoma between 2006 and 2010. Metastatic disease was diagnosed later in 32 cases after a median follow-up of three years (range=1-5.5 years). The median time between the beginning of adjuvant chemotherapy and onset of metastatic disease was 1.7 years (range=0.5-5.5 years). Twenty-eight patients were evaluable for effects of treatment: six patients received FOLFOX plus bevacizumab and 22 FOLFIRI plus bevacizumab. The ORR was 17% in the FOLFOX group versus 36% in the FOLFIRI group (p=0.22). This difference was not statistically significant, despite a trend in favor of FOLFIRI. CONCLUSION: Metastatic disease after exposure to oxaliplatin in the adjuvant setting tends to occur early and can be characterized by partial resistance to this agent. Despite insufficient statistical power, our results suggest that FOLFIRI may result in higher response rates than FOLFOX in this situation. However, oxaliplatin re-challenge can also lead to radiological responses and disease stabilization.

Contemporary outcome and management of patients who had an aborted cystectomy due to unresectable bladder cancer.

OBJECTIVES: Aborted cystectomy due to unresectable disease is not uncommon in patients with bladder cancer. Our aim was to review the outcome of these patients and evaluate various prognostic variables. MATERIALS AND METHODS: Thirty-one bladder cancer patients who underwent aborted radical cystectomy due to unresectable disease from 1993 to 2007, and form the basis of this report. Survival was estimated by the Kaplan and Meier method, with Cox proportional hazards regression model used to evaluate associations between survival and variables studied. RESULTS: Mean age of patients was 66 years with median follow-up of patients alive 10 months. The 2- and 5-year overall survival (OS) was 41% and 0%, respectively. Twenty patients had a pelvic lymph node dissection (PLND) and 11 patients did not. Twenty-three patients received postoperative therapy, of whom 8 received chemotherapy with the intent of surgical consolidation (only 2 were rendered resectable thereafter), and 15 received combined chemoradiation. OS was not significantly associated with hydronephrosis, concomitant CIS, performance status, history of superficial tumors, postoperative therapy, and salvage cystectomy. Patients with pN2-3 had similar overall survival compared with those with pT4b (13 vs. 17 months, P=0.59). However, patients who underwent PLND trended towards improved OS compared with those who did not (24 vs. 10 months, P=0.09). CONCLUSIONS: Outcome of patients with unresectable disease is dismal. Patients who had an aborted cystectomy due to unresectable disease may benefit from PLND. Further refinements of clinical staging to better identify these patients preoperatively and offer them upfront chemotherapy are needed.

Human papillomavirus testing with Pap triage for cervical cancer prevention in Canada: a cost-effectiveness analysis.

BACKGROUND: Recently published results from a large randomized trial (Canadian Cervical Cancer Screening Trial study group) suggest that human papillomavirus testing followed by Pap smear-based triage for human papillomavirus positive women may be an effective way to screen women for cervical cancer. We determined the potential cost-effectiveness of including human papillomavirus tests for cervical cancer screening for Canada and three provinces: Alberta, Newfoundland and Ontario. METHODS: We developed four Markov decision models using data from relevant Canadian and provincial studies and databases. The models were used to determine the number of false positive test results, cancers, lifetime costs and life-expectancy for 27 different screening strategies that varied by age to begin screening (18 or 25 years), screening interval (one, two, three, or five years) and whether the currently recommended strategy (screening every year from age 18 until 21 and then every three years afterwards with conventional Paps) was conducted prior to age 25. Strategies were compared using incremental cost-effectiveness ratios. RESULTS: Screening strategies beginning at age 18 were associated with a substantial increase in the number of false-positive test results but only small differences in the number of cancers compared to the same strategy conducted beginning at age 25. Strategies of human papillomavirus testing first, followed by triage with Pap smears were associated with lower costs and greater increases in life-expectancy than the currently recommended screening strategy in Canada. CONCLUSION: A strategy of human papillomavirus testing beginning at age 25, with Pap triage for women with positive human papillomavirus results may be more effective at reducing cervical cancer at a lower cost than the current recommended strategy for screening in Canada.

Bladder conservation treatment in the elderly population: results and prognostic factors of muscle-invasive bladder cancer.

OBJECTIVES: To report the long-term results of bladder conservation strategies in elderly patients with muscle-invasive bladder cancer and evaluate the different factors affecting locoregional control and patient survival. METHODS: We reviewed the records of 39 elderly patients aged 70 or older, treated with curative intent with radiotherapy, with or without chemotherapy after transurethral resection of bladder for T2-T4aN0 carcinoma of the bladder. Twenty-seven men and 12 women were identified with a median age of 78 (range 70-87). Sixteen of the patients had a previous history of superficial bladder cancer. Twenty-five patients had T2 lesions, 13 patients had T3 lesions, and 1 patient had T4a lesion. The majority of patients were unsuitable for surgery because of medical reasons (67%), whereas the others refused radical cystectomy (33%). Patients were treated with radical radiation therapy with or without chemotherapy. RESULTS: At a median follow-up time of 35.5 months for patients at risk, the 5-year overall survival is 28.9% for all stages, 31.9% for T2 lesions, and 26.8% for T3-T4a lesions. Significant prognostic factors for overall survival on univariate analysis were performance status and age. Five-year cause-specific survival is 37.5% for all stages, 41.5% for T2 lesions, and 34.7% for T3-T4a lesions. No significant prognostic factors for cause-specific survival were indentified on univariate analysis. Toxicity was acceptable. CONCLUSION: Younger age and good performance status were favorable prognostic factors for overall survival. Bladder conservation strategies achieved satisfactory results and were well-tolerated in this elderly population with invasive bladder cancer.

Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analysis of RTOG 99-02.

PURPOSE: Long-term androgen suppression plus radiotherapy (AS+RT) is standard treatment of high-risk prostate cancer. A randomized trial, Radiation Therapy Oncology Group trial 9902, was undertaken to determine whether adjuvant chemotherapy with paclitaxel, estramustine, and etoposide (TEE) plus AS+RT would improve disease outcomes with acceptable toxicity. METHODS AND MATERIALS: High-risk (prostate-specific antigen 20-100 ng/mL and Gleason score >or=7; or Stage T2 or greater, Gleason score 8, prostate-specific antigen level <100 ng/mL) nonmetastatic prostate cancer patients were randomized to AS+RT (Arm 1) vs. AS+RT plus four cycles of TEE (Arm 2). TEE was delivered 4 weeks after RT. AS continued for 2 years for both treatment arms. RT began after 8 weeks of AS began. RESULTS: The Radiation Therapy Oncology Group 9902 trial opened January 11, 2000. Excess thromboembolic toxicity was noted, leading to study closure October 4, 2004. A total of 397 patients were accrued, and the data for 381 were analyzable. An acute and long-term toxicity analysis was performed. The worst overall toxicities during treatment were increased for Arm 2. Of the 192 patients, 136 (71%) on Arm 2 had RTOG Grade 3 or greater toxicity compared with 70 (37%) of 189 patients on Arm 1. Statistically significant increases in hematologic toxicity (p < 0.0001) and gastrointestinal toxicity (p = 0.017) but not genitourinary toxicity (p = 0.07) were noted during treatment. Two Grade 5 complications related to neutropenic infection occurred in Arm 2. Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2. At 2 and 3 years after therapy completion, excess long-term toxicity was not observed in Arm 2. CONCLUSION: TEE was associated with significantly increased toxicity during treatment. The toxicity profiles did not differ at 2 and 3 years after therapy. Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer.

Association between nonsteroidal anti-inflammatory drugs and prostate cancer occurrence.

UNLABELLED: Prostate cancer is the most common malignancy among men in Western nations. Previous studies indicate that nonsteroidal anti-inflammatory drugs have an inhibitory effect on prostate cancer cells. We evaluated the association between frequent use of nonsteroidal anti-inflammatory drugs and prostate cancer occurrence. METHODS: We conducted a nested case-control study using medical administrative databases. All men older than 65 years of age who had filled at least one prescription for nonselective nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors (coxibs), aspirin, or acetaminophen between January 1999 and December 2002 were eligible. Among this group, we identified men who underwent prostate biopsy between January 2000 and June 2002 and did not have a diagnosis of any cancer in the preceding 2-year period. Cases were those with a diagnosis of prostate cancer. Controls were those who did not receive a diagnosis of any cancer. Logistic regression models were used to determine associations between prostate cancer occurrence and frequent exposure (more than 4 months) to nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors or aspirin during the prior 2 years in comparison with no exposure to any of these drugs, adjusting for age and prior finasteride use. RESULTS: We identified 2025 cases and 2150 controls. Older men were at greater risk for developing prostate cancer. Exposure to nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors was associated with a reduced likelihood of prostate cancer (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.58-0.86) as was exposure to aspirin (OR, 0.84; 95% CI, 0.74-0.96). DISCUSSION: Our results suggest that among men 65 years of age or older, frequent use of nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors and use of aspirin are associated with a reduced risk of prostate cancer.

Intermittent androgen ablation in patients with biochemical failure after pelvic radiotherapy for localized prostate cancer.

PURPOSE: To assess the efficacy of intermittent androgen ablation (IAA) in patients with biochemical failure after radiotherapy for prostate cancer. METHODS AND MATERIALS: Thirty-nine patients received a luteinizing hormone-releasing hormone analog every 2 months for a total of 4 doses. IAA was then discontinued if serum prostate-specific antigen (PSA) fell to a normal level with a castrate level of testosterone. Therapy was restarted when the serum PSA level reached > or = 10 ng/mL and was discontinued if hormone resistance or unacceptable toxicity occurred. RESULTS: Median PSA was 9.1 ng/mL at the time of first IAA. The median time between the first and the second cycles was 20.1 months, decreasing to 15.5 months between the third and fourth cycles. Two patients discontinued the treatment because of severe hot flushes. Four patients developed hormone resistance. With a median follow-up of 56.4 months, 5-year survival is 92.3%. Three patients died of unrelated causes. The incidence of distant metastasis is 6.8%. CONCLUSIONS: The use of IAA seems to be a safe and effective treatment for patients with biochemical failure post radiotherapy and no evidence of metastatic disease. The use of IAA limits hormone-related side effects and health care costs without an apparent increase in the risk for the development of metastatic disease.

Association between frequent use of nonsteroidal anti-inflammatory drugs and breast cancer.

BACKGROUND: Eighty percent of all breast cancers and almost 90% of breast cancer deaths occur among post-menopausal women. We used a nested case control design to examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and breast cancer occurrence among women over 65 years of age. The cyclooxygenase (COX)-2 enzyme is expressed more in breast cancers than in normal breast tissue. COX-2 inhibition may have a role in breast cancer prevention. METHODS: In the Canadian province of Quebec, physician services are covered through a governmental insurance plan. Medication costs are covered for those > or = 65 years of age and a publicly funded screening program for breast cancer targets all women 50 years of age or older. We obtained encrypted data from these insurance databases on all women > or = 65 years of age who filled a prescription for COX-2 inhibitors, non-selective NSAIDs (ns-NSAIDs), aspirin, or acetaminophen between January 1998 and December 2002. Cases were defined as those women who have undergone mammography between April 2001 and June 2002 and had a diagnosis of breast cancer within six months following mammography. Controls included those who have undergone mammography between April 2001 and June 2002 without a diagnosis of any cancer during the six months following mammography. The exposure of interest, frequent NSAID use, was defined as use of ns-NSAIDs and/or COX-2 inhibitors for > or = 90 days during the year prior to mammography. Frequent use served as a convenient proxy for long term chronic use. RESULTS: We identified 1,090 cases and 44,990 controls. Cases were older and more likely to have breast cancer risk factors. Logistic regression models adjusting for potential confounders showed that frequent use of ns-NSAIDs and/or COX-2 inhibitors was associated with a lower risk of breast cancer (OR: 0.75, 95% confidence interval 0.64-0.89). Results were similar for COX-2 inhibitors (0.81, 0.68-0.97) and ns-NSAIDs (0.65, 0.43-0.99), when assessed separately. Frequent use of aspirin at doses > 100 mg/day in the year prior to mammography was also associated with a lower risk of breast cancer (0.75, 0.64-0.89). However, use of aspirin at doses < or = 100 mg/day did not have any association with breast cancer (0.91, 0.71-1.16). CONCLUSION: Women who use NSAIDs or doses of aspirin > 100 mg frequently may have a lower risk of breast cancer.

Bayesian modelling of imperfect ascertainment methods in cancer studies.

Tumour registry linkage, chart review and patient self-report are all commonly used ascertainment methods in cancer epidemiology. These methods are used for estimating the incidence or prevalence of different cancer types in a population, and for investigating the effects of possible risk factors for cancer. Tumour registry linkage is often treated as a gold standard, but in fact none of these methods is error free, and failure to adjust for imperfect ascertainment can lead to biased estimates. This is true both if the goal of the study is to estimate the properties of each ascertainment type, or if it is to estimate cancer incidence or prevalence from one or more of these methods. Although rarely applied in the literature to date, when cancer is ascertained by three or more methods, standard latent class models can be used to estimate cancer incidence or prevalence while adjusting for the estimated imperfect sensitivities and specificities of each ascertainment method. These models, however, do not account for variations in these properties across different cancer sites. To address this problem, we extend latent class methodology to include a hierarchical component, which accommodates different ascertainment properties across cancer sites. We apply our model to a data set of 169 lupus patients with three ascertainment methods and eight cancer types. This allows us to estimate the properties of each ascertainment method without assuming any to be a gold standard, and to calculate a standardized incidence ratio for cancer for lupus patients compared to the general population. As our data set is small, we also illustrate the effects as more data become available. We show that our model produces parameter estimates that are substantially different from the currently most popular method of ascertainment, which uses tumour registry data alone.

Breast cancer stage at time of detection in women with systemic lupus erythematosus.

Mounting evidence suggests an increased cancer risk in several autoimmune diseases, including systemic lupus erythematosus (SLE). However, greater scrutiny for cancer in subjects with chronic disease (compared to the general population) might explain this apparent association. If so, one would expect cancers in SLE to be diagnosed at earlier stages than in the general population. This might be particularly evident in cancers where screening is available, such as breast cancer. We linked the University of Pittsburgh lupus cohort with the Pennsylvania Cancer Registry to determine the frequency distribution for stage at diagnosis of invasive breast cancers in the SLE subjects. Data on staging of cancers occurring in the general population of Pennsylvania were obtained from The US Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. A lower percentage of women with SLE presented with localized breast cancer (nine of the 16, 56.2%) compared to the general population of women (63.5%). Although not definitive, this evidence suggests that cancers in SLE are not necessarily diagnosed at earlier stages than in the general population.

Tolerance of radiotherapy and chemotherapy in elderly patients with bladder cancer.

Bladder-sparing radiotherapy with concurrent chemotherapy may be a reasonable alternative to cystectomy in patients with invasive bladder cancer. The purpose of this study was to determine the tolerance of combined treatment in elderly patients. In this retrospective study, the records of patients 70 or more years of age with stage T2-T4a, N0, M0 disease who were treated with bladder-sparing regimens between 1985 and 2000 were examined for toxicity. Of 149 consecutive patients treated for cancer of the bladder, 14 patients met eligibility criteria. The median age was 79 years. At a median follow-up of 17 months, the median survival was 19 months. All patients had at least mild toxicity, with 6 of 14 patients having grade III to IV toxicity. Grade III to IV toxicities included one patient with grade IV neutropenia, three with grade III gastrointestinal toxicities, one patient with grade III urinary frequency, one patient with grade IV ureteral obstruction who required stent placement, and one episode of hydration-induced grade III heart failure. Two of 14 patients stopped chemotherapy and 5 patients required dose reductions for toxicity. The observed rates of toxicity compare favorably with studies of bladder-sparing therapy in patients with median ages less than 70 years. Our study shows that bladder-sparing radiotherapy with concurrent chemotherapy is feasible in patients 70 or more years of age, and should be considered for such patients if they are inoperable or strongly wish to avoid cystectomy.

Do traditional Gail model risk factors account for increased breast cancer in women with lupus?

OBJECTIVE: To determine to what extent the observed experience of breast cancer in a combined cohort of patients with systemic lupus erythematosus (SLE) could be explained by the profile of breast cancer risk factors. METHODS: Data were pooled from 2 centers, the Montreal General Hospital and the Feinberg School of Medicine at Northwestern University in Chicago. For each female cohort member, the probability of developing breast cancer during followup was estimated based on factors (including the individual's age, parity, age at first live birth, age of menarche, personal history of benign breast disease, and family history) using the Gail model, an established model for predicting breast cancer risk. The actual occurrence of cancer cases was determined by linkage with regional cancer registries. RESULTS: Of the 583 women in the combined cohort, 5 had been diagnosed with breast cancer prior to cohort entry, and 14 declined participation. In those remaining, 12 cases of breast cancer occurred compared to 5.6 predicted by the Gail model (standardized incidence ratio 2.1, 95% confidence interval: 1.1, 3.7). Thus, after controlling for risk factors, the incidence of breast cancer was elevated. CONCLUSION: Our data suggest that the risk of breast cancer in our SLE cohort is not completely explained by traditional factors found in the Gail model. Other factors, such as carcinogenic exposures (i.e., alkylating agents and immunosuppressive drugs) or the immunologic dysregulation of SLE itself, may be contributory.

Prevalence of factors influencing cancer risk in women with lupus: social habits, reproductive issues, and obesity.

OBJECTIVE: There is mounting evidence that hematological malignancies are increased in systemic lupus erythematosus (SLE), and the risk of certain solid tumors may also be increased. The pathogenesis may be different for the 2 processes: risk of hematological malignancies in SLE may be due to chronic lymphocyte stimulation, while risk of solid tumors may be influenced by factors such as obesity and reproductive habits. We aimed to determine prevalence in a lupus cohort of selected factors that influence the risk of cancer, and to compare this prevalence to that of the general population. METHODS: Subjects were women followed in the Montreal General Hospital Lupus Clinic. We administered a postal survey of factors known to be associated with lung and aerodigestive cancers (smoking, alcohol use) as well as factors associated with breast and gynecologic cancers (nulliparity, use of oral contraceptives, and hormone replacement therapy). For patients who had died or been lost to followup, data were abstracted from clinic records. Information about nonsteroidal antiinflammatory drug (NSAID) use (a potentially protective factor for colorectal cancer) was also collected. Obesity prevalence was established from the clinic database. Comparison figures were obtained from the 1996-1997 National Population Health Survey data for Quebec women and age adjusted, where possible. RESULTS: Compared to the general population, the lupus population had lower prevalence of current use of oral contraceptives, and greater prevalence of obesity and nulliparity. The average number of pack-years among smokers was also greater in the lupus cohort. CONCLUSION: Solid cancer incidence in SLE may be influenced by established cancer risk factors such as smoking, obesity, and reproductive history.