Novel imaging classification system of nodal disease in human papillomavirus-mediated oropharyngeal squamous cell carcinoma prognostic of patient outcomes.

BACKGROUND: Matted nodes in human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma (OPC) is an independent predictor of distant metastases and decreased overall survival. We aimed to classify imaging patterns of metastatic lymphadenopathy, analyze our classification system for reproducibility, and assess its prognostic value. METHODS: The metastatic lymphadenopathy was classified based on radiological characteristics for 216 patients with HPV-mediated OPC. Patient outcomes were compared and inter-rater reliability was calculated. RESULTS: The presence of ≥3 abutting lymph nodes with imaging features of surrounding extranodal extension (ENE), one subtype of matted nodes, was associated with worse 5-year overall survival, overall recurrence-free survival, regional recurrence-free survival, and distant recurrence-free survival (p ≤ 0.03). Other patterns were not significantly associated with outcome measures. Overall inter-rater agreement was substantial (κ = 0.73). CONCLUSION: One subtype of matted nodes defined by ≥3 abutting lymph nodes with imaging features of surrounding ENE is the radiological marker of worst prognosis.

The effect of statin use on the incidence of prostate cancer: A population-based nested case-control study.

Preclinical studies suggest statins may help prevent prostate cancer (PC), but epidemiologic results are mixed. Many epidemiological studies have relatively short prediagnosis drug exposure data, which may miss some statin use. We completed a nested case-control study investigating the impact of statin use on PC diagnosis and clinically significant PC using data from men aged ≥40 years in the Canadian province of Saskatchewan between 1990 and 2010. Drug exposure histories were derived from a population-based prescription drug database. We used conditional logistic regression to model use of statins as a class and stratified analyses for groups defined by lipophilicity. Clinically significant PC was defined as Gleason score 8-10 OR stage C or D or III or IV at diagnosis. 12,745 cases of PC were risk-set matched on age and geographic location to 50,979 controls. Greater than 90% of subjects had prediagnosis drug exposure histories >15 years. 2,064 (16.2%) cases and 7,956 (15.6%) controls were dispensed one or more statin prescriptions. In multivariable models, ever prescription of statins was not associated with PC diagnosis (OR 0.97; 95% CI 0.90-1.05). Neither lipophilic statins (OR 0.96, 95% CI 0.88-1.04) nor hydrophilic statins (OR 1.06, 95% CI 0.95-1.20) impacted PC diagnosis. There was no effect of the dose or duration of statin use. Diagnosis of clinically significant PC decreased with statin use (OR 0.84, 95% CI 0.73-0.97). Statin use is not associated with overall PC risk, regardless of duration or dose of statin exposure. Statin use is associated with a decreased risk of clinically significant PC.

Secondary Neuroendocrine Carcinoma Following High-Dose Radiotherapy for Head and Neck Cancer: Report of Two Cases.

Patients treated with radiation have an increased risk of developing second cancers, of which carcinomas, sarcomas, and hematological malignancies have most commonly been reported. Neuroendocrine carcinomas (NEC) are rarely reported in patients previously treated with radiation. Two patients, who had successfully undergone chemoradiotherapy for head and neck cancers at our institution, developed secondary NEC within the radiation field more than five years after the treatment. Both patients underwent curative-intent treatment of secondary malignancies, one with chemotherapy, radiation and surgery (Case 1) and the other with chemotherapy and surgery (Case 2). Both had no evidence of disease at a short follow-up of twelve months (Case 1), and three months (Case 2) after treatment. NEC can develop post-radiotherapy; a multidisciplinary approach is necessary to successfully treat these patients.

Solitary Myocardial Metastasis from Locoregionally Controlled Squamous Cell Carcinoma of the Oral Cavity.

We present the case of a 62-year-old male originally diagnosed with squamous cell carcinoma (SCC) of the right retromolar trigone, Stage cT2N2bM0. He was treated radically with a pharyngotomy and segmental mandibular resection, right selective neck nodal dissection, and then reconstruction with a free fibular flap. The pathologic stage was T4aN1. He then received adjuvant chemoradiation therapy with a radiation dose of 6,000 cGy in 30 fractions, along with cisplatin, 100 mg/m(2) every three weeks. Good local control was repeatedly documented for two years. He then presented with shortness of breath and new-onset atrial fibrillation (AF) with rapid ventricular response. Computed tomography/pulmonary embolus protocol (CT/PE) showed no evidence of pulmonary embolism but did show a small pericardial effusion. His AF was refractory to medical management, and he was later admitted to hospital with congestive heart failure. He was found to have a large mass arising from the free wall of the right ventricle, a biopsy of which confirmed squamous cell carcinoma consistent with his head and neck primary. The patient declined further therapy and passed away within one month of presentation. This case is unusual in that the only known site of metastatic disease seen was to the myocardium of the right ventricle, presenting as cardiac arrhythmia and congestive heart failure. Although post-mortem studies show cardiac metastases to occur in 2 to 20% of cancer patients, it is rarely seen as a sole site of relapse in clinical practice.

Treatment outcomes in non-metastatic prostate cancer patients with ultra-high prostate-specific antigen.

PURPOSE: It is commonly believed that prostate cancer patients with very high prostate-specific antigen (PSA) levels are unlikely to benefit from definitive local treatment, and patients with very high PSA are often underrepresented in, or excluded from, randomized clinical trials. Consequently, little is known about their optimal treatment or prognosis. We performed a registry-based analysis of management and outcome in this population of patients. METHODS AND MATERIALS: Our provincial Cancer Registry was used to identify all men who were diagnosed with prostate cancer from 1990 to 2001. A retrospective chart review provided information on stage, Gleason score, PSA at diagnosis, and treatment. In this study, ultra-high PSA was defined as PSA of ≥ 50 ng/ml. For a more complete perspective, treatment outcomes of patients with PSA of 20 to 49.9 ng/ml were also studied. RESULTS: Of the 8378 men diagnosed with prostate cancer during this period, 6,449 had no known nodal or distant metastatic disease. The median follow-up of this group was 67.2 months (range, 0-192 months). A total of 1534 patients had PSA of ≥ 20 ng/ml. Among the 995 patients with PSA 20 to 49.9 ng/ml, 85 had radical prostatectomy (RP), and their 5- and 10-year cause-specific survivals (CSS) were 95% and 84%, respectively. The 497 patients treated with radiotherapy (RT) had 5- and 10-year CSS of 92% and 71%. For the 332 patients with PSA 50-99.9 ng/ml, RT was associated with 5- and 10-year CSS of 81% and 55%. For the 207 patients with PSA of ≥ 100 ng/ml, RT was associated with 5- and 10-year CSS of 80% and 54%. CONCLUSIONS: This is the largest series in the world on non metastatic cancer patients with ultra-high PSA at diagnosis. Even in the setting of a very high presenting PSA level, prostatectomy and radiotherapy are often associated with prolonged survival.

Phase II study of hypofractionated image-guided radiotherapy for localized prostate cancer: outcomes of 55 Gy in 16 fractions at 3.4 Gy per fraction.

PURPOSE: To estimate the late morbidity of a novel, hypofractionated external beam radiotherapy schedule of 55 Gy in 16 fractions (4 fractions/week, 3.4 Gy per fraction) for localized prostate cancer. METHODS AND MATERIALS: A multi-center phase 2 study enrolled seventy-three patients between September 2004 and June 2006. After insertion of fiducial gold markers, they were treated with image-guidance (IGRT) using conformal techniques with intensity-modulation, if necessary, and then followed every 6 months for toxicity rating and PSA. Patient reported outcomes were collected yearly. Median follow up was 4.6 years. RESULTS: At 4 years post-radiotherapy, the cumulative incidence of combined urinary and bowel grade 3 toxicity was 7% (95% CI 3-16%) and grade 2+ was 33% (95% CI 24-46%). All except two patients recovered from their grade 3 events. Patient-reported reduction of function was most pronounced at year two for urinary function (mean -7, SD 16), and at year one for bowel function (mean -7, SD 21). The cumulative incidence of biochemical (PSA nadir+2) or biopsy-proven relapse at 4 years was 9% (95% CI 4-18%). CONCLUSIONS: Hypofractionated radiotherapy is clinically feasible and more convenient than conventional schedules for patients with localized prostate cancer. Phase 3 multicenter studies are on-going (NCT00126165).

Dose-volume analysis of locoregional recurrences in head and neck IMRT, as determined by deformable registration: a prospective multi-institutional trial.

BACKGROUND AND PURPOSE: Although IMRT for head and neck cancer is widely accepted, the implications of sparing normal tissue immediately adjacent to target volumes are not well known. MATERIALS AND METHODS: Between 2002 and 2007, 124 patients with head and neck cancer were treated with surgery and postoperative IMRT (n=79) or definitive RT (n=45). Locoregional recurrences were analyzed for location relative to target volumes, and dosimetry. RESULTS: With a median follow-up of 26.1months, a total of 16 locoregional recurrences were observed. The five-year actuarial locoregional disease-free survival was 82% [95% CI, 72-90%]. Analysis of 18 distinct sites of locoregional failure revealed that five of these failures were within the high dose clinical target volume (CTV), nine failures were at the margin of the CTV, and four recurrences were outside the CTV. The mean dose delivered to these recurrent volumes was 63.1 Gy [range: 57-68 Gy], while the mean dose to the coolest 1cc within each recurrence was 60.0 Gy [range: 51-67 Gy]. There were two periparotid recurrences observed. CONCLUSIONS: We observed excellent locoregional control rates overall. The majority of recurrences occur within high dose regions of the neck and not near the spared parotid glands.

Use of non-steroidal anti-inflammatory drugs and prostate cancer risk: a population-based nested case-control study.

BACKGROUND: Despite strong laboratory evidence that non-steroidal anti-inflammatory drugs (NSAIDs) could prevent prostate cancer, epidemiological studies have so far reported conflicting results. Most studies were limited by lack of information on dosage and duration of use of the different classes of NSAIDs. METHODS: We conducted a nested case-control study using data from Saskatchewan Prescription Drug Plan (SPDP) and Cancer Registry to examine the effects of dose and duration of use of five classes of NSAIDs on prostate cancer risk. Cases (N = 9,007) were men aged ≥40 years diagnosed with prostatic carcinoma between 1985 and 2000, and were matched to four controls on age and duration of SPDP membership. Detailed histories of exposure to prescription NSAIDs and other drugs were obtained from the SPDP. RESULTS: Any use of propionates (e.g., ibuprofen, naproxen) was associated with a modest reduction in prostate cancer risk (Odds ratio = 0.90; 95%CI 0.84-0.95), whereas use of other NSAIDs was not. In particular, we did not observe the hypothesized inverse association with aspirin use (1.01; 0.95-1.07). There was no clear evidence of dose-response or duration-response relationships for any of the examined NSAID classes. CONCLUSIONS: Our findings suggest modest benefits of at least some NSAIDs in reducing prostate cancer risk.

Planning target volume margins for prostate radiotherapy using daily electronic portal imaging and implanted fiducial markers.

BACKGROUND: Fiducial markers and daily electronic portal imaging (EPI) can reduce the risk of geographic miss in prostate cancer radiotherapy. The purpose of this study was to estimate CTV to PTV margin requirements, without and with the use of this image guidance strategy. METHODS: 46 patients underwent placement of 3 radio-opaque fiducial markers prior to prostate RT. Daily pre-treatment EPIs were taken, and isocenter placement errors were corrected if they were > or = 3 mm along the left-right or superior-inferior axes, and/or > or = 2 mm along the anterior-posterior axis. During-treatment EPIs were then obtained to estimate intra-fraction motion. RESULTS: Without image guidance, margins of 0.57 cm, 0.79 cm and 0.77 cm, along the left-right, superior-inferior and anterior-posterior axes respectively, are required to give 95% probability of complete CTV coverage each day. With the above image guidance strategy, these margins can be reduced to 0.36 cm, 0.37 cm and 0.37 cm respectively. Correction of all isocenter placement errors, regardless of size, would permit minimal additional reduction in margins. CONCLUSIONS: Image guidance, using implanted fiducial markers and daily EPI, permits the use of narrower PTV margins without compromising coverage of the target, in the radiotherapy of prostate cancer.

Changes in case mix and treatment patterns in prostate cancer in Saskatchewan during the prostate specific antigen testing era.

BACKGROUND: The prostate specific antigen (PSA) test became available in Saskatchewan in 1990 as a part of the provincial health plan. The purpose of this population-based study was to describe the changes in case mix and treatment patterns for prostate cancer following its introduction. METHODS: The Saskatchewan Cancer Registry was used to identify all new cases of prostate cancer for the period 1985-2001. We reviewed over 10,000 charts to collect information on tumor characteristics, diagnostic methods, and first choice of treatment. This information was linked to the demographic and mortality data from the registry. RESULTS: The age-adjusted incidence of prostate cancer was influenced greatly by PSA testing volumes. Overall, the rate increased from 90.3 per 100,000 in 1985 to 151.3 per 100,000 in 2001. The increase was mostly organ-confined moderately differentiated cases. The incidence rate of metastatic disease dropped about 50% but only in the 70-79 and 80+ age groups. In 1985, 34% of cases were diagnosed by needle biopsy and 60.4% by TURP. In 2001, the values were 76.1% and 19.7%, respectively. More men now choose radical therapy as the first course of treatment, 81% during 1997-2001 compared to only 63.2% in the 1985-1989 period. Mortality rates remained stable in all age groups over these years. CONCLUSION: There have been dramatic changes in the case mix of prostate cancers diagnosed since the introduction of PSA testing in the population and significant changes in clinical management of this disease. Thus far, no changes have occurred in mortality rates in the population.

Analysis of health related quality of life (HRQoL) of patients with clinically localized prostate cancer, one year after treatment with external beam radiotherapy (EBRT) alone versus EBRT and high dose rate brachytherapy (HDRBT).

PURPOSE: Prostate cancer is the leading form of cancer diagnosed among North American men. Most patients present with localized disease, which can be effectively treated with a variety of different modalities. These are associated with widely different acute and late effects, which can be both physical and psychological in nature. HRQoL concerns are therefore important for these patients for selecting between the different treatment options. MATERIALS AND METHODS: One year after receiving radiotherapy for localised prostate cancer 117 patients with localized prostate cancer were invited to participate in a quality of life (QoL) self reported survey. 111 patients consented and participated in the survey, one year after completion of their treatment. 88 patients received EBRT and 23 received EBRT and HDRBT. QoL was compared in the two groups by using a modified version of Functional Assessment of Cancer Therapy-Prostate (FACT-P) survey instrument. RESULTS: One year after completion of treatment, there was no significant difference in overall QoL scores between the two groups of patients. For each component of the modified FACT-P survey, i.e. physical, social/family, emotional, and functional well-being; there were no statistically significant differences in the mean scores between the two groups. CONCLUSION: In prostate cancer patients treated with EBRT alone versus combined EBRT and HDRBT, there was no significant difference in the QoL scores at one year post-treatment.

A randomized controlled trial comparing two educational booklets on prostate cancer.

PURPOSE: To compare the helpfulness of two educational aids or booklets on early-stage prostate cancer. METHOD: Participating consecutive patients and a family member, in three centres, received one of two booklets, one produced by AstraZeneca (AZ), the other produced by us (CCE); the patient and family shared a booklet but were separate study participants. The primary outcome was the Purpose-based Information Assessment completed after participants read their booklet; they rated the importance (4-point Likert scale) of six potential purposes for the information: to help organize their thoughts, understand their situations, decide on treatment, plan, provide emotional support to others, and discuss issues. Each participant then rated how helpful their booklet was (4-point Likert scale) in addressing each purpose they had rated above the lowest importance category. Participants mailed in their responses. RESULTS: Complete data were received from 308 (81%) of those who consented to the study: 152 in the CCE group and 156 in the AZ group. The CCE booklet was read for a longer time [chi(2) = 28.61, p = 0.00] but was easier to find information in chi(2) = 7.6, p = 0.05]. Although for each purpose, most readers rated each booklet in one of the top two (of four) helpfulness categories, the CCE booklet was rated more helpful for: organizing [chi(2) = 30.49, p = 0.00], understanding [chi(2) = 12.07, p = .007], deciding [chi(2) = 9.96, p = 0.02] and planning [chi(2) = 18.67, p = 0.00]. CONCLUSIONS: High helpfulness ratings of both booklets suggest that patients benefit from education aids while differences in the booklet ratings suggest that aids are not equally helpful. The CCE booklet, the more helpful booklet of this study, is a systematically developed education aid available to urologists in Canada.

Twenty-year follow-up study of long-term survival of limited-stage small-cell lung cancer and overview of prognostic and treatment factors.

PURPOSE: To predict the long-term survival results of clinical trials earlier than using actuarial methods and to assess the factors predictive of long-term cure in patients with limited-stage small-cell lung cancer. METHODS AND MATERIALS: Between 1981 and 1998, 1417 new cases of small-cell lung cancer were diagnosed in Saskatchewan, Canada, of which 244 were limited stage and treated with curative intent. They were followed to the end of February 2002. A parametric lognormal statistical model was retrospectively validated to determine whether long-term survival rates could be estimated several years earlier than is possible using the standard life-table actuarial method. RESULTS: The survival time of the uncured group followed a lognormal distribution. Four 2-year periods of diagnosis were combined, and patients were followed as a cohort for an additional 2 years. The estimated 10-year cause-specific survival rate was 13% by the lognormal model. The Kaplan-Meier calculation for 10-year cause-specific survival rate was 15% +/- 3%. The data also showed that the absence of mediastinal lymphadenopathy and higher chest radiotherapy dose were significant prognostic factors on multivariate analysis (p < 0.05). Among the 163 patients given prophylactic cranial irradiation, a higher biologically effective dose to the brain did not improve survival or decrease the incidence of brain metastases. CONCLUSION: The lognormal model has been validated for the estimation of survival in patients with limited-stage small-cell lung cancer. A higher biologically effective dose to the brain did not improve survival or decrease the incidence of brain metastases.

Evaluation of a question-and-answer booklet on early-stage prostate-cancer.

A question-and-answer booklet about early-stage prostate-cancer was created for patients and their family members. Two sequential studies were conducted to determine if the single source of information would be useful to both patients and their families. The first study used 1:1 interviews with 11 readers (6 patients and 5 family members) to identify features of the booklet that may be problematic. In all, six features were identified as either irrelevant or problematic in their design. The second study was a survey of 54 patients (79% response rate) and 33 family members (49% response rate); the study was designed to obtain an overall evaluation of the booklet, to clarify the proportion of readers for whom the features identified in the first study were problematic, to provide insight into how and why readers were reading the booklet, and to determine if patients and family differed on any of the outcomes. Results showed that 85% of readers liked the booklet; most (81.6%) read it from beginning to end. Most readers in both groups wanted the information to help them understand (85.2% patients; 87.9% family); more patients than family wanted it for treatment decision making (44.4% patients; 27.3% family) and for planning (35.2% patients; 9.1% family); more family (42.4%) than patients (20.4%) wanted the information to help them provide support. We conclude that even though patients and family differ in why they want information, the booklet appears to be considered useful by both groups.

Prophylactic cranial irradiation revisited: cost-effectiveness and quality of life in small-cell lung cancer.

PURPOSE: To investigate the therapeutic usefulness and cost-effectiveness of prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (SCLC) who had achieved a complete remission. METHODS: A retrospective chart review was undertaken of all patients diagnosed in Saskatchewan with SCLC between 1987 and 1998 inclusive. Patients who achieved a complete remission were divided into two groups, depending on whether they underwent PCI (PCI+ and PCI-, respectively). The quality-of-life-adjusted survival was estimated by the Q-TWiST method (quality time without symptoms and toxicity). The mean incremental costs per month of incremental OS were calculated in a cost-effectiveness analysis. RESULTS: Among the 98 complete remission patients, the median OS for PCI+ and PCI- patients was 20.0 and 19.0 months, respectively (p > 0.05, nonsignificant). The median disease-free survival was 14.7 and 10.0 months, respectively (p < 0.05). The difference in the mean Q-TWiST survival was significant (p < 0.01). The mean marginal cost was $18,834/PCI+ patient and $17,885/PCI- patient (p > 0.05, nonsignificant). The cost-effectiveness ratio was $70/mo of incremental OS if u(tox) and u(rel) (the utility coefficients to reflect the value of time in health states of toxicity and relapse) were assumed to be 1.0. CONCLUSION: PCI is a cost-effective treatment that improves the quality-of-life-adjusted survival for patients with a complete remission of SCLC.