Ashesh B. Jani

An electronic application for rapidly calculating Charlson comorbidity score

BackgroundUncertainty regarding comorbid illness, and ability to tolerate aggressive therapy has led to minimal enrollment of elderly cancer patients into clinical trials and often substandard treatment. Increasingly, comorbid illness scales have proven useful in identifying subgroups of elderly patients who are more likely to tolerate and benefit from aggressive therapy. Unfortunately, the use of such scales has yet to be widely integrated into either clinical practice or clinical trials research.MethodsThis article reviews evidence for the validity of the Charlson Comorbidity Index (CCI) in oncology and provides a Microsoft Excel (MS Excel) Macro for the rapid and accurate calculation of CCI score. The interaction of comorbidity and malignant disease and the validation of the Charlson Index in oncology are discussed.ResultsThe CCI score is based on one year mortality data from internal medicine patients admitted to an inpatient setting and is the most widely used comorbidity index in oncology. An MS Excel Macro file was constructed for calculating the CCI score using Microsoft Visual Basic. The Macro is provided for download and dissemination.The CCI has been widely used and validated throughout the oncology literature and has demonstrated utility for most major cancers. The MS Excel CCI Macro provides a rapid method for calculating CCI score with or without age adjustments. The calculator removes difficulty in score calculation as a limitation for integration of the CCI into clinical research. The simple nature of the MS Excel CCI Macro and the CCI itself makes it ideal for integration into emerging electronic medical records systems.ConclusionsThe increasing elderly population and concurrent increase in oncologic disease has made understanding the interaction between age and comorbid illness on life expectancy increasingly important. The MS Excel CCI Macro provides a means of increasing the use of the CCI scale in clinical research with the ultimate goal of improving determination of optimal treatments for elderly cancer patients.

Concurrent Chemotherapy and Intensity-Modulated Radiation Therapy for Anal Canal Cancer Patients: A Multicenter Experience

PURPOSE To report a multicenter experience treating anal canal cancer patients with concurrent chemotherapy and intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS From October 2000 to June 2006, 53 patients were treated with concurrent chemotherapy and IMRT for anal squamous cell carcinoma at three tertiary-care academic medical centers. Sixty-two percent were T1-2, and 67% were N0; eight patients were HIV positive. Forty-eight patients received fluorouracil (FU)/mitomycin, one received FU/cisplatin, and four received FU alone. All patients underwent computed tomography-based treatment planning with pelvic regions and inguinal nodes receiving a median of 45 Gy. Primary sites and involved nodes were boosted to a median dose of 51.5 Gy. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. All late toxicity was scored using Radiation Therapy Oncology Group criteria. RESULTS Median follow-up was 14.5 months (range, 5.2 to 102.8 months). Acute grade 3+ toxicity included 15.1% GI and 37.7% dermatologic toxicity; all acute grade 4 toxicities were hematologic; and acute grade 4 leukopenia and neutropenia occurred in 30.2% and 34.0% of patients, respectively. Treatment breaks occurred in 41.5% of patients, lasting a median of 4 days. Forty-nine patients (92.5%) had a complete response, one patient had a partial response, and three had stable disease. All HIV-positive patients achieved a complete response. Eighteen-month colostomy-free survival, overall survival, freedom from local failure, and freedom from distant failure were 83.7%, 93.4%, 83.9%, and 92.9%, respectively. CONCLUSION Preliminary outcomes suggest that concurrent chemotherapy and IMRT for anal canal cancers is effective and tolerated favorably compared with historical standards.

Early prostate cancer: clinical decision-making

Prostate cancer is one of the most common malignant diseases for which health-care intervention is sought worldwide, and in many developed countries it is the most common. Some patients with early-stage prostate cancer, especially those who are elderly and have comorbidities, can be observed without treatment. Surgery (radical prostatectomy) and radiotherapy (external-beam radiotherapy, brachytherapy, or both) are the most widely accepted curative options for patients with early-stage disease who need intervention. All these local treatments have been refined, resulting in comparable cure rates; however, they all have different side-effect profiles. Adjuvant systemic treatments (hormones or chemotherapy), which are effective for advanced-stage disease, might have a greater role in early-stage disease. Selecting the best option for individuals from the available options is challenging--the decision on whether and how to treat is based on many disease and patient factors. Here, we review the major treatment options, discuss their relative advantages and disadvantages, and provide a general approach to management of patients with early-stage prostate cancer.

The impact of age and comorbidity on survival outcomes and treatment patterns in prostate cancer.

The management of localized prostate cancer is based on stage, grade, PSA, and subjective assessment of comorbidity and life expectancy. Over the last 15 y, stage migration and the improved use of Gleason sum, PSA and TNM staging have led to many treatment options for patients with newly diagnosed localized prostate cancer. At the same time, advances in treatment techniques have helped decrease the long-term complications of surgery and radiotherapy. However, the importance of age and comorbidity, in survival outcomes and treatment decision-making has been largely overlooked. Currently, stage, grade, and PSA are the only quantifiable variables consistently used in research and treatment decision-making. Comorbidity and life expectancy have remained largely subjective variables. Increasing longevity and a rapidly aging population have made age and comorbidity increasingly important factors in clinical research and treatment decision-making. This article reviews the importance of age and comorbidity on treatment decisions and survival outcomes in prostate cancer, as well as their use as objectively quantifiable variables. Examples from the general oncology literature are given. The overview also examines validated comorbidity indices and advocates the use of the Charlson Comorbidity Index (CCI) in research outcomes and treatment decision-making in prostate cancer. Several clinical vignettes are provided to demonstrate the potential clinical utility of the CCI as applied to prostate cancer.

Comparison of late gastrointestinal and genitourinary toxicity of prostate cancer patients undergoing intensity-modulated versus conventional radiotherapy using localized fields

To compare late genitourinary (GU) and gastrointestinal (GI) toxicity of radiotherapy (RT) to localized fields for prostate cancer delivered using intensity-modulated RT (IMRT) versus conventional RT (ConvRT). The records of 461 patients were reviewed; 355 patients received IMRT and 106 received ConvRT. Late GU and GI toxicity were compared. Late GU toxicity rates were not significantly different (P=0.166); however, late GI toxicity rates were lower with IMRT (P=0.001). Regression analyses demonstrated that only IMRT use (P=0.006) predicted reduction in late GI toxicity but no factors correlated with late GU toxicity. IMRT did not influence late GU toxicity but was associated with a reduction of late GI toxicity over ConvRT.

A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Retinol Palmitate (Vitamin A) for Symptomatic Chronic Radiation Proctopathy

PURPOSEThis study was designed to determine whether oral retinol palmitate (vitamin A) can reduce the symptoms of radiation proctopathy.METHODSA randomized, double-blind trial comparing retinol palmitate (10,000 IU by mouth for 90 days) to placebo was conducted. Eligible patients were more than six months postpelvic radiotherapy and had significant symptoms as measured with the Radiation Proctopathy System Assessments Scale. Nineteen patients were randomized in total: ten to retinol palmitate and nine to placebo. The Radiation Proctopathy System Assessments Scale scores before and every 30 days for 90 days were measured. Five placebo nonresponders were crossed over to the retinol palmitate for another 90 days. Response was defined as a reduction in two or more symptoms by at least two Radiation Proctopathy System Assessments Scale points.RESULTSSeven of ten retinol palmitate patients responded, whereas two of nine responded to placebo (P = 0.057). Mean pre-post-treatment change in Radiation Proctopathy System Assessments Scale (Δ Radiation Proctopathy System Assessments Scale) in the retinol palmitate group was 11 ± 5, whereas Δ Radiation Proctopathy System Assessments Scale in the placebo group was 2.5 ± 3.6 (P = 0.013, Mann-Whitney U test). Additionally, all five placebo nonresponders who were crossed over to treatment with retinal palmitate responded to treatment.CONCLUSIONSIn our trial, retinol palmitate significantly reduced rectal symptoms of radiation proctopathy, perhaps because of wound-healing effects. The current results can serve as the foundation for future trials examining retinol palmitate in the multi-institutional setting.

Changing face and different countenances of prostate cancer: Racial and geographic differences in prostate-specific antigen (PSA), stage, and grade trends in the PSA era

The purpose of this investigation was to examine changes in pretreatment prostate‐specific antigen (PSA), stage, and grade over the past decade as a function of race and geographic region. A multiinstitutional database representing 6,790 patients (1,417 African‐American, 5,373 white) diagnosed with nonmetastatic prostate cancer between 1988 and 1997 was constructed. PSA, stage, and grade data were tabulated by calendar year and region, and time trend analyses based on race and region were performed. There was an overall decline of PSA of 0.8%/year, which was significant (P = 0.0001), with a faster rate of decline in African‐Americans (1.9%/year) than for whites (0.6%/year). The odds ratio (OR) for a stage shift was 1.09, which was significant (P < 0.0001), and this shift was greater in whites. The OR for an overall grade shift was 1.15, which was significant (P < 0.0001). Although grade and PSA trends were similar for the different regions, there were significant regional differences in stage trends. The implications are that the face of prostate cancer has changed over the past decade; i.e., the distributions of stage, grade, and PSA (the most important prognosticators) have changed. In addition, the countenances of that face are different for whites and African‐Americans. For African‐Americans, this is good news: the stage, grade, and PSA distributions are more favorable now than before. For whites, the trends are more complex and more dependent on region. These findings should be used for future clinical and health‐policy decisions in the screening and treatment of prostate cancer.

Biological-effective versus conventional dose volume histograms correlated with late genitourinary and gastrointestinal toxicity after external beam radiotherapy for prostate cancer: a matched pair analysis.

BackgroundTo determine whether the dose-volume histograms (DVHs) for the rectum and bladder constructed using biological-effective dose (BED-DVHs) better correlate with late gastrointestinal (GI) and genitourinary (GU) toxicity after treatment with external beam radiotherapy for prostate cancer than conventional DVHs (C-DVHs).MethodsThe charts of 190 patients treated with external beam radiotherapy with a minimum follow-up of 2 years were reviewed. Six patients (3.2%) were found to have RTOG grade 3 GI toxicity, and similarly 6 patients (3.2%) were found to have RTOG grade 3 GU toxicity. Average late C-DVHs and BED-DVHs of the bladder and rectum were computed for these patients as well as for matched-pair control patients. For each matched pair the following measures of normalized difference in the DVHs were computed: (a) δAUC = (Area Under Curve [AUC] in grade 3 patient – AUC in grade 0 patient)/(AUC in grade 0 patient) and (b) δV60 = (Percent volume receiving = 60 Gy [V60] in grade 3 patient – V60 in grade 0 patient)/(V60 in grade 0 patient).ResultsAs expected, the grade 3 curve is to the right of and above the grade 0 curve for all four sets of average DVHs – suggesting that both the C-DVH and the BED-DVH can be used for predicting late toxicity. δAUC was higher for the BED-DVHs than for the C-DVHs – 0.27 vs 0.23 (p = 0.036) for the rectum and 0.24 vs 0.20 (p = 0.065) for the bladder. δV60 was also higher for the BED-DVHs than for the C-DVHs – 2.73 vs 1.49 for the rectum (p = 0.021) and 1.64 vs 0.71 (p = 0.021) for the bladder.ConclusionsWhen considering well-established dosimetric endpoints used in evaluating treatment plans, BED-DVHs for the rectum and bladder correlate better with late toxicity than C-DVHs and should be considered when attempting to minimize late GI and GU toxicity after external beam radiotherapy for prostate cancer.

Hormone therapy adjuvant to external beam radiotherapy for locally advanced prostate carcinoma: a complication-adjusted number-needed-to-treat analysis.

Hormone therapy commonly is used to treat metastatic, locally advanced, and localized prostate carcinoma. The objective of the current investigation was to determine, using the number‐needed‐to‐treat (NNT) method, the effect of using hormone therapy to treat locally advanced disease, with consideration given to both the complications and the known advantages associated with hormone therapy.

Influence of intensity-modulated radiotherapy on acute genitourinary and gastrointestinal toxicity in the treatment of localized prostate cancer.

The objective of this investigation is to compare acute genitourinary (GU) and gastrointestinal (GI) toxicity results of radiotherapy to localized fields delivered using intensity-modulated radiotherapy (IMRT) versus conventional radiotherapy (ConvRT). The records of 481 consecutive prostate cancer patients receiving RT to localized fields at a single institution were reviewed; 108 received IMRT and 373 received ConvRT. Acute GU and GI toxicity, as defined by the Radiation Therapy Oncology Group (RTOG) grading system, were compared using the chi-square test. Ordered logit regression analyses were performed using all major disease and treatment factors as covariates. Acute GU grade 0, 1, 2, 3, and 4 toxicity rates were 23%, 40%, 34%, 3%, and 0%, respectively, in the IMRT cohort and 31%, 37%, 30%, 1%, and 1%, respectively, in the ConvRT cohort - these rates were not significantly different (p=0.118). Acute GI grade 0, 1, 2, 3, and 4 toxicity rates were 42%, 37%, 22%, 0%, and 0%, respectively, in the IMRT cohort and 33%, 32%, 35%, 0%, and 0%, respectively, in the ConvRT cohort - this lower toxicity in the IMRT group was significant (p=0.013). The regression analyses showed that only IMRT use (p=0.046) predicted reduction in acute GI toxicity but no factors correlated with acute GU toxicity rate. In conclusion, in our retrospective single-institution analysis, IMRT was not associated with reduction of acute GU toxicity but was associated with a reduction of acute GI toxicity over ConvRT in the treatment of prostate cancer to localized fields.