Toxicity and efficacy of salvage carbon 11-choline positron emission tomography/computed tomography-guided radiation therapy in patients with lymph node recurrence of prostate cancer.

OBJECTIVE: To report the 3-year toxicity and outcomes of carbon 11 (11C)-choline-positron emission tomography (PET)/computed tomography (CT)-guided radiotherapy (RT), delivered via helical tomotherapy (HTT; Tomotherapy® Hi-Art II® Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node (LN) relapses in patients with prostate cancer. PATIENTS AND METHODS: From January 2005 to March 2013, 81 patients with biochemical recurrence after surgery, with or without adjuvant/salvage RT or radical RT, and with evidence of LN 11C-choline-PET/CT pathological uptake, underwent HTT (median [range] prostate-specific antigen level 2.59 [0.61-187] ng/mL). Of the 81 patients, 72 were treated at the pelvic and/or lumbar-aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C-choline-PET/CT. Nine patients were treated without simultaneous integrated boost (50-65.5 Gy, 25-30 fr). RESULTS: With a median (range) follow-up of 36 (9-116) months, 91.4% of the patients had a PSA reduction 3 months after HTT. The 3-year overall, local relapse-free and clinical relapse-free survival rates were 80.0, 89.8 and 61.8%, respectively. The 3-year actuarial incidences of ≥grade 2 rectal and ≥grade 2 genitourinary toxicity were 6.6% (±2.9%) and 26.3% (±5.5%), respectively. A PSA nadir of ≥0.26 ng/mL (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7-7.7; P = 0.001), extrapelvic 11C-choline-PET/CT-positive LN location (HR 2.4, 95% CI 0.9-6.4; P = 0.07), RT previous to HTT (HR 2.7; 95% CI 1.07-6.9, P = 0.04) and number of positive LNs (HR 1.13, 95% CI 1.04-1.22; P = 0.003) were the main predictors of clinical relapse after HTT. CONCLUSIONS: 11C-choline-PET/CT-guided HTT is safe and effective in the treatment of LN relapses of prostate cancer in previously treated patients.

Salvage therapy of small volume prostate cancer nodal failures: a review of the literature.

New imaging modalities may be useful to identify prostate cancer patients with small volume, limited nodal relapse ("oligo-recurrent") potentially amenable to local treatments (radiotherapy, surgery) with the aim of long-term control of the disease, even in a condition traditionally considered prognostically unfavorable. This report reviews the new diagnostic tools and the main published data about the role of surgery and radiation therapy in this particular subgroup of patients.

Clinical factors predicting late severe urinary toxicity after postoperative radiotherapy for prostate carcinoma: a single-institute analysis of 742 patients.

PURPOSE: To investigate the clinical factors independently predictive of long-term severe urinary sequelae after postprostatectomy radiotherapy. PATIENTS AND METHODS: Between 1993 and 2005, 742 consecutive patients underwent postoperative radiotherapy with either adjuvant (n = 556; median radiation dose, 70.2 Gy) or salvage (n = 186; median radiation dose, 72 Gy) intent. RESULTS: After a median follow-up of 99 months, the 8-year risk of Grade 2 or greater and Grade 3 late urinary toxicity was almost identical (23.9% vs. 23.7% and 12% vs. 10%) in the adjuvant and salvage cohorts, respectively. On univariate analysis, acute toxicity was significantly predictive of late Grade 2 or greater sequelae in both subgroups (p <.0001 in both cases), and hypertension (p = .02) and whole-pelvis radiotherapy (p = .02) correlated significantly in the adjuvant cohort only. The variables predictive of late Grade 3 sequelae were acute Grade 2 or greater toxicity in both groups and whole-pelvis radiotherapy (8-year risk of Grade 3 events, 21% vs. 11%, p = .007), hypertension (8-year risk, 18% vs. 10%, p = .005), age ≤ 62 years at RT (8-year risk, 16% vs. 11%, p = .04) in the adjuvant subset, and radiation dose >72 Gy (8-year risk, 19% vs. 6%, p = .007) and age >71 years (8-year risk, 16% vs. 6%, p = .006) in the salvage subgroup. Multivariate analysis confirmed the independent predictive role of all the covariates indicated as statistically significant on univariate analysis. CONCLUSIONS: The risk of late Grade 2 or greater and Grade 3 urinary toxicity was almost identical, regardless of the RT intent. In the salvage cohort, older age and greater radiation doses resulted in a worse toxicity profile, and younger, hypertensive patients experienced a greater rate of severe late sequelae in the adjuvant setting. The causes of this latter correlation and apparently different etiopathogenesis of chronic damage in the two subgroups were unclear and deserve additional investigation.

Anatomical and clinical predictors of acute bowel toxicity in whole pelvis irradiation for prostate cancer with Tomotherapy.

PURPOSE: Assessing predictors of acute bowel toxicity after whole-pelvis irradiation (WPRT) Image-guided Tomotherapy with simultaneous integrated boost on prostate/prostate bed. METHODS AND MATERIALS: In the period March 2005-April 2009, 178 patients were treated with radical or adjuvant/salvage intent with WPRT Tomotherapy. Median dose to the pelvic nodes was 51.8 Gy/28 fractions while concomitantly delivering 65.5-74.2 Gy to prostate/prostatic bed. The impact of many anatomical and clinical parameters on ≥ Grade 2 acute bowel toxicity was investigated by logistic analyses. RESULTS: Only 15/178 patients (8.4%) experienced Grade 2 toxicity (none Grade 3). Main predictors at univariate analysis were nodal CTV (CTVN ≥ 380 cc; OR: 3.7, p=0.017), treatment duration (< 40 days; OR: 6.2, p=0.006) and Grade 2 acute rectal toxicity (OR: 6.5, p=0.015). A multivariate analysis including only pre-treatment variables revealed an independent role of CTVN and age; if including treatment-related factors the best predictors were age, treatment duration and Grade 2 rectal toxicity. This last was correlated with the overlap between PTVN and loops (OVPN ≥ 51 cc; OR: 14.4, p=0.0003) that is representative of the volume of loops receiving the prescribed dose (51.8 Gy, 1.85 Gy/fr). CONCLUSIONS: Acute bowel toxicity after WPRT Tomotherapy is mild, relatively rare and associated to larger CTVN and older age. While efforts to further reduce it do not appear to be relevant, the pre-treatment assessment of "high-risk" patients may help physicians in better managing symptoms. A prospective validation would be very important in confirming these results and in better refining dose-volume bowel effects including symptoms milder that the ones here investigated and retrospectively assessed.

Consolidation radiotherapy for a rare case of extranodal mucosa-associated lymphoid tissue non-Hodgkin's lymphoma synchronous with prostate adenocarcinoma.

Nongastric primary extranodal mucosa-associated lymphoid tissue (MALT) lymphomas are uncommon, with around 0.1% occurring in the prostate. Even less frequent is the presence of MALT lymphoma synchronous with another type of neoplasm in the same organ, especially the prostate. Only a single case of concurrent adenocarcinoma and MALT lymphoma of the prostate has been reported in the literature. We report a rare case of primary extranodal marginal zone MALT lymphoma incidentally diagnosed during radical prostatectomy for an adenocarcinoma of the prostate in a 53-year-old patient. Fourteen months later a recurrence of the MALT lymphoma involving both sides of the diaphragm was found and was treated with chemoimmunotherapy. High-dose radiotherapy was delivered to residual bulky disease in the pelvic region. At 18 months from the end of radiation treatment the patient was without signs of relapse of MALT lymphoma. This preliminary result confirms that rare cases of MALT lymphoma of the prostate should be discussed and treated under the collaborative supervision of hematologists and medical and radiation oncologists. In fact, at an advanced stage of the disease, a chemotherapy regimen with additional consolidation radiotherapy could be an effective strategy, as in all other lymphomas.

Inflammatory pseudotumor of mediastinum treated with tomotherapy and monitored with FDG-PET/CT: case report and literature review.

Mediastinal inflammatory pseudotumor is a rare disease with reactive pseudoneo-plastic features and a proven capacity for local invasion. The radiographic appearance of inflammatory pseudotumor is quite non-specific and the definitive diagnosis is based on the histological evaluation of tissue specimens. Resection of the lesion is the treatment of choice. However, nonsurgical treatments such as radiotherapy and steroids have been employed in the setting of incomplete surgical resection, tumor recurrence, and patients being unfit for surgery. The case described here is being reported because of the rare mediastinal location and atypical treatment approach including salvage irradiation and monitoring with FDG-PET/CT. Because of the irregular target volume inside the mediastinum as defined by FDG-PET/CT and the significant pulmonary comorbidity, it was deemed necessary to optimize dose delivery with intensity-modulated radiation therapy (IMRT). A possible gain by means of daily control of patient setup with image-guided radiation therapy was also hypothesized and we used tomotherapy to irradiate the lesion. The first FDG-PET/CT after treatment confirmed further reduction of the metabolic activity followed by stable disease in the mediastinum, with no new occurrence of disease 16, 24 and 30 months after tomotherapy.