Gita Suneja

Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose–volume outcome relationships

Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearmans rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

Elevated Cancer-Specific Mortality Among HIV-Infected Patients in the United States

PURPOSE Despite advances in the treatment of HIV, HIV-infected people remain at increased risk for many cancers, and the number of non-AIDS-defining cancers is increasing with the aging of the HIV-infected population. No prior study has comprehensively evaluated the effect of HIV on cancer-specific mortality. PATIENTS AND METHODS We identified cases of 14 common cancers occurring from 1996 to 2010 in six US states participating in a linkage of cancer and HIV/AIDS registries. We used Cox regression to examine the association between patient HIV status and death resulting from the presenting cancer (ascertained from death certificates), adjusting for age, sex, race/ethnicity, year of cancer diagnosis, and cancer stage. We included 1,816,461 patients with cancer, 6,459 (0.36%) of whom were HIV infected. RESULTS Cancer-specific mortality was significantly elevated in HIV-infected compared with HIV-uninfected patients for many cancers: colorectum (adjusted hazard ratio [HR], 1.49; 95% CI, 1.21 to 1.84), pancreas (HR, 1.71; 95% CI, 1.35 to 2.18), larynx (HR, 1.62; 95% CI, 1.06 to 2.47), lung (HR, 1.28; 95% CI, 1.17 to 1.39), melanoma (HR, 1.72; 95% CI, 1.09 to 2.70), breast (HR, 2.61; 95% CI, 2.06 to 3.31), and prostate (HR, 1.57; 95% CI, 1.02 to 2.41). HIV was not associated with increased cancer-specific mortality for anal cancer, Hodgkin lymphoma, or diffuse large B-cell lymphoma. After further adjustment for cancer treatment, HIV remained associated with elevated cancer-specific mortality for common non-AIDS-defining cancers: colorectum (HR, 1.40; 95% CI, 1.09 to 1.80), lung (HR, 1.28; 95% CI, 1.14 to 1.44), melanoma (HR, 1.93; 95% CI, 1.14 to 3.27), and breast (HR, 2.64; 95% CI, 1.86 to 3.73). CONCLUSION HIV-infected patients with cancer experienced higher cancer-specific mortality than HIV-uninfected patients, independent of cancer stage or receipt of cancer treatment. The elevation in cancer-specific mortality among HIV-infected patients may be attributable to unmeasured stage or treatment differences as well as a direct relationship between immunosuppression and tumor progression.

Disparities in the treatment and outcomes of lung cancer among HIV-infected individuals

Objectives:HIV-infected people have elevated risk for lung cancer and higher mortality following cancer diagnosis than HIV-uninfected individuals. It is unclear whether HIV-infected individuals with lung cancer receive similar cancer treatment as HIV-uninfected individuals. Design/methods:We studied adults more than 18 years of age with lung cancer reported to the Texas Cancer Registry (N = 156 930) from 1995 to 2009. HIV status was determined by linkage with the Texas enhanced HIV/AIDS Reporting System. For nonsmall cell lung cancer (NSCLC) cases, we identified predictors of cancer treatment using logistic regression. We used Cox regression to evaluate effects of HIV and cancer treatment on mortality. Results:Compared with HIV-uninfected lung cancer patients (N = 156 593), HIV-infected lung cancer patients (N = 337) were more frequently young, non-Hispanic black, men, and with distant stage disease. HIV-infected NSCLC patients less frequently received cancer treatment than HIV-uninfected patients [60.3 vs. 77.5%; odds ratio 0.39, 95% confidence interval (CI) 0.30–0.52, after adjustment for diagnosis year, age, sex, race, stage, and histologic subtype]. HIV infection was associated with higher lung cancer-specific mortality (hazard ratio 1.34, 95% CI 1.15–1.56, adjusted for demographics and tumor characteristics). Inclusion of cancer treatment in adjusted models slightly attenuated the effect of HIV on lung cancer-specific mortality (hazard ratio 1.25; 95% CI 1.06–1.47). Also, there was a suggestion that HIV was more strongly associated with mortality among untreated than among treated patients (adjusted hazard ratio 1.32 vs. 1.16, P-interaction = 0.34). Conclusion:HIV-infected NSCLC patients were less frequently treated for lung cancer than HIV-uninfected patients, which may have affected survival.

Cancer Treatment Disparities in HIV-Infected Individuals in the United States

PURPOSE HIV-infected individuals with cancer have worse survival rates compared with their HIV-uninfected counterparts. One explanation may be differing cancer treatment; however, few studies have examined this. PATIENTS AND METHODS We used HIV and cancer registry data from Connecticut, Michigan, and Texas to study adults diagnosed with non-Hodgkins lymphoma, Hodgkins lymphoma, or cervical, lung, anal, prostate, colorectal, or breast cancers from 1996 to 2010. We used logistic regression to examine associations between HIV status and cancer treatment, adjusted for cancer stage and demographic covariates. For a subset of local-stage cancers, we used logistic regression to assess the relationship between HIV status and standard treatment modality. We identified predictors of cancer treatment among individuals with both HIV and cancer. RESULTS We evaluated 3,045 HIV-infected patients with cancer and 1,087,648 patients with cancer without HIV infection. A significantly higher proportion of HIV-infected individuals did not receive cancer treatment for diffuse large B-cell lymphoma (DLBCL; adjusted odds ratio [aOR], 1.67; 95% CI, 1.41 to 1.99), lung cancer (aOR, 2.18; 95% CI, 1.80 to 2.64), Hodgkins lymphoma (aOR, 1.77; 95% CI, 1.33 to 2.37), prostate cancer (aOR, 1.79; 95% CI, 1.31 to 2.46), and colorectal cancer (aOR, 2.27; 95% CI, 1.38 to 3.72). HIV infection was associated with a lack of standard treatment modality for local-stage DLBCL (aOR, 2.02; 95% CI, 1.50 to 2.72), non-small-cell lung cancer (aOR, 2.43; 95% CI, 1.46 to 4.03), and colon cancer (aOR, 4.77; 95% CI, 1.76 to 12.96). Among HIV-infected individuals, factors independently associated with lack of cancer treatment included low CD4 count, male sex with injection drug use as mode of HIV exposure, age 45 to 64 years, black race, and distant or unknown cancer stage. CONCLUSION HIV-infected individuals are less likely to receive treatment for some cancers than uninfected people, which may affect survival rates.

Trends in primary central nervous system lymphoma incidence and survival in the U.S.

It is suspected that primary central nervous system lymphoma (PCNSL) rates are increasing among immunocompetent people. We estimated PCNSL trends in incidence and survival among immunocompetent persons by excluding cases among human immunodeficiency virus (HIV)‐infected persons and transplant recipients. PCNSL data were derived from 10 Surveillance, Epidemiology and End Results (SEER) cancer registries (1992–2011). HIV‐infected cases had reported HIV infection or death due to HIV. Transplant recipient cases were estimated from the Transplant Cancer Match Study. We estimated PCNSL trends overall and among immunocompetent individuals, and survival by HIV status. A total of 4158 PCNSLs were diagnosed (36% HIV‐infected; 0·9% transplant recipients). HIV prevalence in PCNSL cases declined from 64·1% (1992–1996) to 12·7% (2007–2011), while the prevalence of transplant recipients remained low. General population PCNSL rates were strongly influenced by immunosuppressed cases, particularly in 20–39 year‐old men. Among immunocompetent people, PCNSL rates in men and women aged 65+ years increased significantly (1·7% and 1·6%/year), but remained stable in other age groups. Five‐year survival was poor, particularly among HIV‐infected cases (9·0%). Among HIV‐uninfected cases, 5‐year survival increased from 19·1% (1992–1994) to 30·1% (2004–2006). In summary, PCNSL rates have increased among immunocompetent elderly adults, but not in younger individuals. Survival remains poor for both HIV‐infected and HIV‐uninfected PCNSL patients.

Effect of Practice Integration Between Urologists and Radiation Oncologists on Prostate Cancer Treatment Patterns

PURPOSE National attention has focused on whether urology-radiation oncology practice integration, known as integrated prostate cancer centers, contributes to the use of intensity modulated radiation therapy, a common and expensive prostate cancer treatment. MATERIALS AND METHODS We examined prostate cancer treatment patterns before and after conversion of a urology practice to an integrated prostate cancer center in July 2006. Using the SEER (Statistics, Epidemiology and End Results)-Medicare database, we identified patients 65 years old or older in 1 statewide registry diagnosed with nonmetastatic prostate cancer between 2004 and 2007. We classified patients into 3 groups, including 1--those seen by integrated prostate cancer center physicians (exposure group), 2--those living in the same hospital referral region who were not seen by integrated prostate cancer center physicians (hospital referral region control group) and 3--those living elsewhere in the state (state control group). We compared changes in treatment among the 3 groups, adjusting for patient, clinical and socioeconomic factors. RESULTS Compared with the 8.1 ppt increase in adjusted intensity modulated radiation therapy use in the state control group, the use of this therapy increased 20.3 ppts (95% CI 13.4, 27.1) in the integrated prostate cancer center group and 19.2 ppts (95% CI 9.6, 28.9) in the hospital referral region control group. Androgen deprivation therapy, for which Medicare reimbursement decreased sharply, similarly decreased in integrated prostate cancer center and hospital referral region controls. Prostatectomy decreased significantly in the integrated prostate cancer center group. CONCLUSIONS Coincident with the conversion of a urology group practice to an integrated prostate cancer center, we observed an increase in intensity modulated radiation therapy and a decrease in androgen deprivation therapy in patients seen by integrated prostate cancer center physicians and those seen in the surrounding health care market that were not observed in the remainder of the state.

Prevalence of HIV infection among U.S. Hodgkin lymphoma cases

Background: Hodgkin lymphoma is uncommon in the U.S. general population; however, Hodgkin lymphoma risk is elevated in people with human immunodeficiency virus (HIV) infection. Thus, despite the low HIV prevalence in the United States, the HIV epidemic may have contributed substantially to the general population burden of Hodgkin lymphoma. Methods: We used data from 14 U.S. cancer registries in the Surveillance, Epidemiology, and End Results Program that recorded HIV status of Hodgkin lymphoma cases at diagnosis during 2000 to 2010. We computed the HIV prevalence in Hodgkin lymphoma cases by demographic and tumor characteristics, the proportion of deaths among Hodgkin lymphoma cases because of HIV, and 5-year mortality by HIV status. Results: Of 22,355 Hodgkin lymphoma cases, 848 (3.79%) were HIV infected at diagnosis. HIV prevalence in Hodgkin lymphoma cases was greater among males than females (6.0% vs. 1.2%). Among males, HIV prevalence was greatest among 40- to 59-year-olds (14.2%), non-Hispanic blacks (16.9%), Hispanics (9.9%), and among cases of lymphocyte-depleted (15.1%), and mixed cellularity Hodgkin lymphoma (10.5%). Eight percent of male and 1.5% of female Hodgkin lymphoma cases died from HIV. Five-year mortality was two-fold higher in HIV-infected Hodgkin lymphoma cases (36.9% vs. 17.5%). Conclusion: In the United States, a substantial proportion of lymphocyte-depleted and mixed cellularity Hodgkin lymphoma cases and Hodgkin lymphoma cases among non-Hispanic black, Hispanic, and middle-aged men are HIV infected. In addition, HIV is an important cause of death among Hodgkin lymphoma cases. Impact: Clinicians should be aware of the high prevalence of HIV in certain subgroups of patients with Hodgkin lymphoma and routine HIV testing should be recommended for all patients presenting with Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev; 23(2); 274–81. ©2013 AACR.

Acute toxicity of proton beam radiation for pediatric central nervous system malignancies

Proton beam therapy (PBT) for pediatric CNS malignancies may reduce late toxicity, but acute toxicity is not well defined. We examined acute toxicity for children with CNS malignancies treated with PBT.

Addressing the growing cancer burden in the wake of the AIDS epidemic in Botswana: The BOTSOGO collaborative partnership.

Botswana has experienced a dramatic increase in HIV-related malignancies over the past decade. The BOTSOGO collaboration sought to establish a sustainable partnership with the Botswana oncology community to improve cancer care. This collaboration is anchored by regular tumor boards and on-site visits that have resulted in the introduction of new approaches to treatment and perceived improvements in care, providing a model for partnership between academic oncology centers and high-burden countries with limited resources.

Cancer Incidence following Expansion of HIV Treatment in Botswana.

Background The expansion of combination antiretroviral treatment (ART) in southern Africa has dramatically reduced mortality due to AIDS-related infections, but the impact of ART on cancer incidence in the region is unknown. We sought to describe trends in cancer incidence in Botswana during implementation of the first public ART program in Africa. Methods We included 8479 incident cases from the Botswana National Cancer Registry during a period of significant ART expansion in Botswana, 2003–2008, when ART coverage increased from 7.3% to 82.3%. We fit Poisson models of age-adjusted cancer incidence and counts in the total population, and in an inverse probability weighted population with known HIV status, over time and estimated ART coverage. Findings During this period 61.6% of cancers were diagnosed in HIV-infected individuals and 45.4% of all cancers in men and 36.4% of all cancers in women were attributable to HIV. Age-adjusted cancer incidence decreased in the HIV infected population by 8.3% per year (95% CI -14.1 to -2.1%). However, with a progressively larger and older HIV population the annual number of cancers diagnosed remained constant (0.0% annually, 95% CI -4.3 to +4.6%). In the overall population, incidence of Kaposi’s sarcoma decreased (4.6% annually, 95% CI -6.9 to -2.2), but incidence of non-Hodgkin lymphoma (+11.5% annually, 95% CI +6.3 to +17.0%) and HPV-associated cancers increased (+3.9% annually, 95% CI +1.4 to +6.5%). Age-adjusted cancer incidence among individuals without HIV increased 7.5% per year (95% CI +1.4 to +15.2%). Interpretation Expansion of ART in Botswana was associated with decreased age-specific cancer risk. However, an expanding and aging population contributed to continued high numbers of incident cancers in the HIV population. Increased capacity for early detection and treatment of HIV-associated cancer needs to be a new priority for programs in Africa.