How can men destined for biochemical failure after androgen deprivation and radiotherapy be identified earlier?

PURPOSE: The significance of prostate-specific antigen (PSA) increases during the recovery of androgen after androgen deprivation therapy (ADT) and radiotherapy for prostate cancer is not well understood. This study sought to determine whether the initial PSA increase from undetectable after completion of all treatment predicts for eventual biochemical failure (BF). METHODS AND MATERIALS: Between July 1992 and March 2004, 163 men with a Gleason score of 8-10 or initial PSA level >20 ng/mL, or Stage T3 prostate cancer were treated with radiotherapy (median dose, 76 Gy) and ADT and achieved an undetectable PSA level. The first detectable PSA level after the cessation of ADT was defined as the PSA sentinel rise (SR). A PSA-SR of >0.25, >0.5, >0.75, and >1.0 ng/mL was studied as predictors of BF (nadir plus 2 ng/mL). Cox proportional hazards models were used for univariate and multivariate analyses for BF adjusting for pretreatment differences in Gleason score, stage, PSA level (continuous), dose (continuous), and ADT duration (<12 vs. > or = 12 months). RESULTS: Of the 163 men, 41 had BF after therapy. The median time to BF was 25 months (range, 4-96). The 5-year BF rate stratified by a PSA-SR of < or = 0.25 vs. >0.25 ng/mL was 28% vs. 43% (p = 0.02), < or = 0.5 vs. >0.5 ng/mL was 30% vs. 56% (p = 0.0003), < or = 0.75 vs. >0.75 ng/mL was 29% vs. 66% (p < 0.0001), and < or = 1.0 vs. >1.0 ng/mL was 29% vs. 75% (p < 0.0001). All four PSA-SRs were independently predictive of BF on multivariate analysis. CONCLUSION: The PSA-SR predicts for BF. A PSA-SR of >0.5 ng/mL can be used for early identification of men at greater risk of BF.

A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or (125)I permanent implant.

PURPOSE: To compare the toxicity and biochemical outcomes of intensity-modulated radiation therapy (IMRT) and (125)I transperineal permanent prostate seed implant ((125)I) for patients with low-risk prostate cancer. METHODS AND MATERIALS: Between 1998 and 2004, a total of 374 low-risk patients (prostate-specific antigen < 10 ng/ml, T1c-T2b, Gleason score of 6 or less, and no neoadjuvant hormones) were treated at Fox Chase Cancer Center (216 IMRT and 158 (125)I patients). Median follow-up was 43 months for IMRT and 48 months for (125)I. The IMRT prescription dose ranged from 74-78 Gy, and (125)I prescription was 145 Gy. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was recorded by using a modified Radiation Therapy Oncology Group scale. Freedom from biochemical failure was defined by using the Phoenix definition (prostate-specific antigen nadir + 2.0 ng/ml). RESULTS: Patients treated by using IMRT were more likely to be older and have a higher baseline American Urological Association symptom index score, history of previous transurethral resection of the prostate, and larger prostate volumes. On multivariate analysis, IMRT was an independent predictor of lower acute and late Grade 2 or higher GU toxicity and late Grade 2 or higher GI toxicity. Three-year actuarial estimates of late Grade 2 or higher toxicity were 2.4% for GI and 3.5% for GU by using IMRT compared with 7.7% for GI and 19.2% for GU for (125)I, respectively. Four-year actuarial estimates of freedom from biochemical failure were 99.5% for IMRT and 93.5% for (125)I (p = 0.09). CONCLUSIONS: The IMRT and (125)I produce similar outcomes, although IMRT appears to have less acute and late toxicity.

The proportion of prostate biopsy tissue with Gleason pattern 4 or 5 predicts for biochemical and clinical outcome after radiotherapy for prostate cancer.

PURPOSE: To investigate the prognostic utility of the proportion of prostate biopsy tissue containing Gleason pattern 4 or 5 (GP4/5) after definitive radiotherapy (RT) for prostate cancer. METHODS AND MATERIALS: A total of 568 patients with T1c-3 Nx/0 prostate cancer who received three-dimensional conformal RT alone between May 1989 and August 2001 were studied. There were 161 men with Gleason score 7-10 disease. The GP4/5 was defined as the percentage of biopsy tissue containing Gleason pattern 4 or 5. A Cox proportional hazards model was used for univariate and multivariate analyses (MVA) for biochemical failure (BF) (American Society of Therapeutic Radiology and Oncology definition) and distant metastasis (DM). A recursive partitioning analysis was done using the results of the MVA to identify a cutpoint for GP4/5. RESULTS: The median follow-up was 46 (range, 13-114) months and median RT dose was 76 (range, 65-82) Gy. On MVA, increasing initial prostate-specific antigen (p = 0.0248) decreasing RT dose (continuous, p = 0.0022), T stage (T1/2 vs. T3), (p = 0.0136) and GP4/5 (continuous, p < 0.0001) were significant predictors of BF in a model also containing GS. GP4/5 was the only significant predictor of DM in the same model (p < 0.0001). CONCLUSION: The GP4/5 in prostate biopsy specimens is a predictor of BF and DM after RT independent of Gleason score. This parameter should be reported by the pathologist when reviewing prostatic biopsy specimens.

Stereotactic body radiotherapy for early-stage non-small cell lung cancer: clinical outcomes from a National Patient Registry.

OBJECTIVES: Stereotactic body radiotherapy (SBRT) is a definitive local treatment option for patients with stage I non-small cell lung cancer (NSCLC) who are not surgical candidates and patients who refuse surgery. The purpose of this study was to assess the impact of SBRT on T1-T2 NSCLC from a national registry, reflecting practices and outcomes in a real-world setting. METHODS: The RSSearch® Patient Registry was screened for T1-T2N0M0 NSCLC patients treated from May 2004 to May 2013 with SBRT. Descriptive analyses were used for patient, tumor, and treatment characteristics. Overall survival (OS) and local control (LC) were calculated using the Kaplan-Meier method. RESULTS: In total, 723 patients with 517 T1 and 224 T2 lesions were treated with SBRT. Median follow-up was 12 months (1-87 months) with a median age of 76 years. Median SBRT dose was 54 Gy (range 10-80 Gy) delivered in a median of 3 fractions (range 1-5), and median biological equivalent dose (BED10) was 151.2 Gy (range 20-240 Gy). Median OS was 30 and 26 months for T1 and T2 tumors, respectively (p = 0.019). LC was associated with higher BED10 for T2 tumors, but not in T1 tumors at a median follow-up of 17 months. Seventeen-month LC for T2 tumors treated with BED10 < 105 Gy, BED10 105-149, and BED10 ≥ 150 Gy was 43, 74, and 95 %, respectively (p = 0.011). Local failure rates for T2 tumors treated with BED10 < 105 Gy, 105-149 Gy, and ≥150 Gy were 32, 21, and 8 % (p = 0.029), respectively. Median OS for patients with T2 tumors treated with BED10 < 105 Gy was 17 vs. 32 months for T2 tumors treated with BED10 105-149 Gy (p = 0.062). CONCLUSION: SBRT for T1-T2 NSCLC is feasible and effective in the community setting. OS was greater for patients with T1 lesions compared to T2 lesions. An improvement in LC was observed in patients with T2 lesions treated with BED10 > 105 Gy.

Impact of neck dissection on long-term feeding tube dependence in patients with head and neck cancer treated with primary radiation or chemoradiation.

BACKGROUND: The impact of posttreatment neck dissection on prolonged feeding tube dependence in patients with head and neck squamous cell cancer (HNSCC) treated with primary radiation or chemoradiation remains unknown. METHODS: We conducted a retrospective cohort study using propensity score adjustment to investigate the effect of neck dissection on prolonged feeding tube dependence. RESULTS: A review of 67 patients with node-positive HNSCC (T1-4N1-3), treated with primary radiation or chemoradiation, with no evidence of tumor recurrence and follow-up of at least 24 months, was performed. Following adjustment for covariates, the relative risk (RR) of feeding tube dependence at 18 months was significantly increased in patients treated with posttreatment neck dissection (RR 4.74, 95% confidence interval [CI] 2.07-10.89). At 24 months, the relative risk of feeding tube dependence in the patients having undergone neck dissection increased further (RR 7.66, 95% CI 2.07-10.89). Of patients with feeding tubes 2 years after completing treatment, 75% remained feeding tube dependent. CONCLUSION: Neck dissection may contribute to chronic oropharyngeal dysphagia in HNSCC patients treated with primary radiation or chemoradiation.

Does transurethral resection of prostate (TURP) affect outcome in patients who subsequently develop prostate cancer?

OBJECTIVES: Pretreatment prostate specific antigen (PSA) is a strong predictor of prostate cancer outcome after radiotherapy and is a key parameter in pretreatment risk assessment. Because PSA is secreted from both benign and malignant tissue, a prior transurethral resection of prostate (TURP) may lower pretreatment PSA levels out of proportion to the extent of cancer. The purpose of this study was to determine whether a history of TURP is associated with increased biochemical failure (BF) after definitive radiotherapy for prostate cancer. METHODS: From April 1989 to October 2001, 1135 men with low to intermediate risk T1c-2NX/0M0 (2002 AJCC) prostate cancer with a pretreatment PSA less than 20 ng/mL received three-dimensional conformal radiotherapy (median dose, 76 Gy) without androgen deprivation. The median pretreatment PSA was 7.4 ng/mL (range, 0.4 to 19.9). There were 126 men with a prior history of TURP. The Cox proportional hazards model was used for univariate and multivariate analyses for BF (nadir + 2 ng/mL definition). RESULTS: On multivariable analysis, Gleason score (GS), PSA, and T-stage were significant predictors of BF in a model containing TURP and dose. A history of TURP was not a significant independent predictor of BF on subgroup analysis. There was a trend toward significance for the subgroup of GS less than 7 (P = 0.12). CONCLUSIONS: A history of prior TURP does not affect outcome after RT for prostate cancer in low to intermediate risk patients.

Does treatment duration affect outcome after radiotherapy for prostate cancer?

PURPOSE: The protraction of external beam radiotherapy (RT) time is detrimental in several disease sites. In prostate cancer, the overall treatment time can be considerable, as can the potential for treatment breaks. We evaluated the effect of elapsed treatment time on outcome after RT for prostate cancer. METHODS AND MATERIALS: Between April 1989 and November 2004, 1,796 men with prostate cancer were treated with RT alone. The nontreatment day ratio (NTDR) was defined as the number of nontreatment days divided by the total elapsed days of RT. This ratio was used to account for the relationship between treatment duration and total RT dose. Men were stratified into low risk (n = 789), intermediate risk (n = 798), and high risk (n = 209) using a single-factor model. RESULTS: The 10-year freedom from biochemical failure (FFBF) rate was 68% for a NTDR <33% vs. 58% for NTDR >/=33% (p = 0.02; BF was defined as a prostate-specific antigen nadir + 2 ng/mL). In the low-risk group, the 10-year FFBF rate was 82% for NTDR <33% vs. 57% for NTDR >/=33% (p = 0.0019). The NTDR was independently predictive for FFBF (p = 0.03), in addition to T stage (p = 0.005) and initial prostate-specific antigen level (p < 0.0001) on multivariate analysis, including Gleason score and radiation dose. The NTDR was not a significant predictor of FFBF when examined in the intermediate-risk group, high-risk group, or all risk groups combined. CONCLUSIONS: A proportionally longer treatment duration was identified as an adverse factor in low-risk patients. Treatment breaks resulting in a NTDR of >/=33% (e.g., four or more breaks during a 40-fraction treatment, 5 d/wk) should be avoided.

Unexpected dementia following prophylactic cranial irradiation for small cell lung cancer: case report.

OBJECT: Prophylactic cranial irradiation (PCI) is commonly offered to patients with limited stage primary small cell lung cancer following a complete response. METHODS: We present the unique case of a 76-year-old woman treated with PCI with a dose of 30 Gy in 15 fractions, at 200 cGy per fraction who developed progressive dementia. CONCLUSIONS: This is the first reported case of dementia from PCI at this low dose per fraction. Patients need to be counseled regarding the risks and benefits of treatment, including dementia with treatment and risk of sequelae from CNS metastasis without treatment. The authors review the data supporting PCI and the incidence of radiation associated dementia.