Predicting post-external beam radiation therapy PSA relapse of prostate cancer using pretreatment MRI.

PURPOSE: To investigate whether pretreatment endorectal magnetic resonance imaging (MRI) findings can predict biochemical relapse in patients with clinically localized prostate cancer treated with external beam radiation therapy (EBRT). METHODS AND MATERIALS: Between January 2000 and January 2002, 224 patients (median age, 69 years; age range, 45-82 years) with biopsy-proven prostate cancer underwent endorectal MRI before high-dose (≥81Gy) EBRT. The value of multiple clinical and MRI variables in predicting prostate-specific antigen (PSA) relapse at 5 years was determined by use of univariate and multivariate stepwise Cox regression. Clinical variables included pretreatment PSA, clinical T stage, Gleason score, use of neoadjuvant hormonal therapy, and radiation dose. Magnetic resonance imaging variables, derived from retrospective consensus readings by two radiologists, were used to measure intraprostatic and extraprostatic tumor burden. RESULTS: After a median follow-up of 67 months, PSA relapse developed in 37 patients (16.5%). The significant predictors of PSA relapse on univariate analysis were pretreatment PSA, clinical T stage, and multiple MRI variables, including MRI TN stage score; extracapsular extension (ECE) status; number of sextants involved by ECE, all lesions, or index (dominant) lesion; apical involvement; and diameter and volume of index lesion. Pretreatment PSA and ECE status were the only significant independent predictors on multivariate analysis (p < 0.05 for both). Extracapsular extension status was associated with the highest hazard ratio, 3.04; 5-year PSA relapse rates were 7% for no ECE, 20% for unilateral ECE, and 48% for bilateral ECE. CONCLUSIONS: Magnetic resonance imaging findings can be used to predict post-EBRT PSA relapse, with ECE status on MRI and pretreatment PSA being significant independent predictors of this endpoint.

Long-term neck control rates after complete response to chemoradiation in patients with advanced head and neck cancer.

OBJECTIVES: To examine the long-term neck failure outcome in patients with advanced head and neck cancer treated on larynx/organ preservation protocols at Memorial Sloan-Kettering Cancer Center. MATERIALS AND METHODS: Two hundred thirteen patients were enrolled from 1983 through 1995 on larynx/organ preservation protocols receiving induction chemotherapy followed by radiotherapy alone or with concomitant chemotherapy. Eighty-six patients with node-positive disease received definitive chemoradiotherapy at Memorial Sloan-Kettering Cancer Center. A median dose of 70 Gy was delivered. The median follow-up of the surviving patients was 9 years. RESULTS: Sixty-five patients with node-positive disease achieved a clinical complete response and were observed after chemoradiation without immediate neck dissection. The crude rate of subsequent neck failure among those patients according to initial nodal classification was: N1 14% (3 of 21), N2: 15% (6 of 40), N3: 0% (0 of 4). The median overall survival of these patients was: N1: 12.2 years; N2: 6.5 years; N3: 0.8 years. Patients who experienced a complete response to induction chemotherapy in the neck had improved overall survival (53% vs. 29%; P = 0.005) and a lower incidence of neck failure (10% vs. 24%; P = 0.14) when compared with those patients who had less than a complete response. CONCLUSIONS: Our data suggests that in patients with advanced neck disease who have a clinical complete response in the neck to chemoradiation long-term neck control is 85% or greater without neck dissection. Whether functional imaging or treatment response to induction chemotherapy would provide better discrimination of the 10% to 15% who may experience neck relapse is an important question for future research initiatives.

Primary central nervous system lymphoma: the role of consolidation treatment after a complete response to high-dose methotrexate-based chemotherapy.

BACKGROUND: The most effective treatment for a new diagnosis of primary central nervous system lymphoma is high-dose methotrexate (MTX)-based chemotherapy followed by whole-brain radiation therapy (WBRT). However, this combined modality treatment carries an increased risk of delayed neurotoxicity. For patients who achieve a complete response (CR) after induction that uses high-dose MTX-based chemotherapy, it is not clear if consolidation treatment is necessary. Therefore, a retrospective study was conducted to assess the impact of consolidation treatment after a CR to initial induction chemotherapy on disease control and survival. METHODS: The authors retrospectively analyzed 122 patients who achieved a CR after initial MTX-based chemotherapy. The benefit of consolidation WBRT, high-dose cytarabine (HDAC), or both on failure-free (FFS) and overall survival (OS) was assessed. RESULTS: With a median follow-up of 60 months, FFS was longer in patients who received WBRT plus HDAC as consolidation treatment (P = .03 by univariate analysis); there was no difference in OS observed among patients who received no consolidation treatment, HDAC alone, WBRT plus HDAC, or WBRT alone. Age and Karnofsky performance scale (KPS) were the only independent prognostic factors. Patients who received WBRT alone or in combination with HDAC had higher rates of neurotoxicity. CONCLUSIONS: Consolidation treatment with WBRT, HDAC, or both does not appear to improve survival in patients who achieved a CR with induction MTX-based therapy. Age, KPS, and risk of delayed neurotoxicity must be considered in the choice of consolidation regimens.

Delayed neurotoxicity in primary central nervous system lymphoma.

BACKGROUND: Treatment for primary central nervous lymphoma (PCNSL) with chemotherapy and radiotherapy has resulted in improved survival, but some patients develop neurologic deterioration that represents a treatment-related toxic effect. This delayed neurotoxicity has been poorly defined in the literature, and the underlying mechanisms are unknown. OBJECTIVE: To describe the clinical findings, time course, and pathophysiologic mechanisms associated with neurotoxicity in an attempt to generate hypotheses for future studies that address prevention and treatment of this complication of successful PCNSL therapy. DESIGN: Retrospective review. SETTING: Department of Neurology, Memorial Sloan-Kettering Cancer Center. PATIENTS: One hundred eighty-five patients treated for PCNSL, including 43 who developed neurotoxicity. MAIN OUTCOME MEASURES: Potential risk factors, clinical course, and neuropsychological, neuroimaging, and histologic findings. RESULTS: The 5-year cumulative incidence of neurotoxicity was 24%; this incidence increases over time. Neurotoxicity presented as a rapidly progressive subcortical dementia characterized by psychomotor slowing, executive and memory dysfunction, behavioral changes, gait ataxia, and incontinence. Imaging findings revealed diffuse white matter disease and cortical-subcortical atrophy. Available autopsy data showed white matter damage with gliosis, thickening of small vessels, and demyelination. Statistical analyses were performed, accounting for death as a competing risk. Older age (P = .01), mental status changes at diagnosis (P = .04), female sex (P = .05), and radiotherapy (P<.001) predicted neurotoxicity on univariate analysis, but only radiotherapy remained significant in the multivariate setting. CONCLUSION: These findings suggest that the core pathophysiologic mechanism is the interruption of frontal-subcortical circuits mediated by radiation damage, possibly caused by progressive microvascular alterations, loss of oligodendrocyte progenitors, or oxidative stress.

T1 adenocarcinoma of the rectum: transanal excision or radical surgery?

BACKGROUND: Recent studies suggest local excision may be acceptable treatment of T1 adenocarcinoma of the rectum, but there is little comparative data with radical surgery to assess outcomes and quantify risk. We performed a retrospective evaluation of patients with T1 rectal cancers treated by either transanal excision or radical resection at our institution to assess patient selection, cancer recurrence, and survival. METHODS: All patients who underwent surgery for T1 adenocarcinomas of the rectum (0-15 cm from anal verge) by either transanal excision (TAE) or radical resection (RAD) between January 1987 and January 2004 were identified from a prospective database. Data were analyzed using Fisher exact test, Kaplan-Meier method, and log-rank test. RESULTS: Three hundred nineteen consecutive patients with T1 lesions were treated by transanal excision (n = 151) or radical surgery (n = 168) over the 17-year period. RAD surgery was associated with higher tumor location in the rectum, slightly larger tumor size, a similar rate of adverse histology, and a lymph node metastasis rate of 18%. Despite these features, patients who underwent RAD surgery had fewer local recurrences, fewer distant recurrences, and significantly better recurrence-free survival (P = 0.0001). Overall and disease-specific survival was similar for RAD and TAE groups. CONCLUSION: Despite a similar risk profile in the 2 surgical groups, patients with T1 rectal cancer treated by local excision were observed to have a 3- to 5-fold higher risk of tumor recurrence compared with patients treated by radical surgery. Local excision should be reserved for low-risk cancers in patients who will accept an increased risk of tumor recurrence, prolonged surveillance, and possible need for aggressive salvage surgery. Radical resection is the more definitive surgical treatment of T1 rectal cancers.