[en] Purpose: A critical determinant of prognosis in prostate cancer is grade of disease. Historically, this has been determined by biopsy of the prostate using transperineal, transrectal, or transurethral approaches. Several reports in the literature reveal that these biopsies often underestimate the histologic grade of the tumor when compared with subsequent radical prostatectomy specimens. Methods and Materials: Data from the literature were analyzed to assess the magnitude of this bias towards undergrading. Grade of biopsy specimens (well-differentiated = Gleason score 2-4; moderately differentiated = Gleason 5-7; poorly differentiated = Gleason 8-10) were correlated with the ultimate prostatectomy grade. Analysis was made of tendency to undergrade specimens using strict criteria of data inclusion for needle biopsies, and more relaxed criteria for all types of prostate biopsies. Results: Grading accuracy from needle biopsies was 71%, with 23% undergraded and 6% overgraded. A chi-square test on equal chance of under- vs. overgrading yielded p = 0.022. Grading accuracy from needle, open perineal, and transurethral biopsies was 65%, with 23% undergraded and 12% overgraded. A similar chi-square test yielded p = 0.007. In both cases, there appears to exist a significant bias towards undergrading. Conclusions: In addition to other well-documented factors that confound comparisons between radiation therapy and surgical series in carcinoma of the prostate, grade migration exists as well. The equivalence of radiation therapy and surgery with respect to overall survival in this disease is accomplished despite these biases

[en] Objective: Institutional policy in the 1970's and 80's dictated that patients with potentially curable prostate cancer undergo PLND prior to definitive XRT. Our group has reported 80% 15-year actuarial cause-specific survival for the 147 patients so treated. Analysis was made of PSA values and clinical outcomes of patients who were clinically without evidence of disease (NED) 10 years after a negative staging pelvic lymphadenectomy and definitive radiation therapy (XRT) for prostate cancer. Materials and Methods: One hundred patients underwent staging pelvic lymphadenectomy between 11/1/74 and 1/1/86, of which 98 had pathologically negative lymph nodes (N₀). These patients subsequently underwent definitive radiotherapy; a median dose of 66.6 Gy (range 63-70.2 Gy) was delivered. Forty-two N₀ patients with sufficient follow-up were alive and clinically NED 10 years post-operatively. None of these patients had ever received hormonal therapy. Distribution by disease stage at diagnosis was: Stage A2: 12 pts; Stage B: 19 pts; Stage B2/ C: 6 pts; Stage C: 5 pts. Median follow-up was 12 years 4 months, with a minimum follow-up of 10 years. Results: Of the 42 NED survivors at 10 years, 5 pts died subsequently without PSA data, remaining clinically NED (median 13y 3m post-operatively); 37 patients were alive and without evidence of disease off all therapy at 10 years post-operatively. Most recent PSA data reveal: Bone scans were performed on the 8 patients with elevated PSA. These revealed a single patient with diffuse but asymptomatic bone metastases. Ultrasound-guided sextant biopsies were performed on one 78-year-old patient with elevated PSA 19 years post-operatively, revealing an asymptomatic local recurrence. Conclusions: Radiation therapy delivered to a surgically staged population of prostate cancer patients contributes to normalization of PSA in 78% ((29(37))) of patients with ≥10 year follow-up. Most of these patients will have PSA levels ≤ 1.5 ng/ml. More critically, however, patients clinically NED at 10 years have a low likelihood of clinical failure, even in the presence of PSA values between 4.0 and 10 ng/ml. In these patients, PSA trends are of greater utility than absolute values

[en] Purpose: The clinical late effects of intraoperative radiotherapy (IORT) on peripheral nerve were investigated in a foxhound model. Methods and Materials: Between 1982 and 1987, 40 animals underwent laparotomy with intraoperative radiotherapy of doses from 0-75 Gy administered to the right lumbosacral plexus. Subsequently, all animals were monitored closely and sacrificed to assess clinical effects to peripheral nerve. This analysis reports final clinical results of all animals, with follow-up to 5 years. Results: All animals treated with ≥ 25 Gy developed ipsilateral neuropathy. An inverse relationship was noted between intraoperative radiotherapy dose and time to neuropathy, with an effective dose for 50% paralysis (ED₅₀) of 17.2 Gy. One of the animals treated with 15 Gy IORT developed paralysis, after a much longer latency than the other animals. Conclusions: Doses of 15 Gy delivered intraoperatively may be accompanied by peripheral neuropathy with long-term follow-up. This threshold is less than that reported with shorter follow-up. The value of ED₅₀ determined here is in keeping with data from other animal trials, and from clinical trials in humans

[en] An accurate, simple and time-saving sector integration method for calculating the proton output (dose/monitor unit, MU) is presented based on the following treatment field parameters: aperture shape, aperture size, measuring position, beam range and beam modulation. The model is validated with dose/MU values for 431 fields previously measured at our center. The measurements were obtained in a uniform scanning proton beam with a parallel plate ionization chamber in a water phantom. For beam penetration depths of clinical interest (6-27 cm water), dose/MU values were measured as a function of spread-out Bragg peak (SOBP) extent and aperture diameter. First, 90 randomly selected fields were used to derive the model parameters, which were used to compute the dose/MU values for the remaining 341 fields. The min, max, average and the standard deviation of the difference between the calculated and the measured dose/MU values of the 341 fields were used to evaluate the accuracy and stability, for different energy ranges, aperture sizes, measurement positions and SOBP values. The experimental results of the five different functional sets showed that the calculation model is accurate with calculation errors ranging from -2.4% to 3.3%, and 99% of the errors are less than ±2%. The accuracy increases with higher energy, larger SOBP and bigger aperture size. The average error in the dose/MU calculation for small fields (field size <25 cm²) is 0.31 ± 0.96 (%). (note)

[en] Previous reports establish low risk of complications in pediatric treatments under anesthesia/sedation (A/S) in the outpatient setting. Here, we present our institutional experience with A/S by age and gender in children receiving daily proton RT. After Institutional Review Board approval, we reviewed our center’s records between 9/9/2004 and 6/30/2013 with respect to age and gender of A/S requirement in our pediatric patients (defined as patients ≤18 years of age). Of 390 patients treated in this era, 182 were girls. Children aged ≤3 invariably required A/S; and by age 7–8, approximately half of patients do not. For pediatric patients ≥ 12 years of age, approximately 10% may require A/S for different reasons. There was no difference by gender. Beyond age 3, the requirement for A/S decreases in an age-dependent fashion, with a small cadre of older children having difficulty enough with sustained immobilization that A/S is necessary. In our experience, there is no difference in A/S requirement by gender

[en] To evaluate acute toxicity endpoints in a cohort of patients receiving head and neck radiation with proton therapy or intensity modulated radiation therapy (IMRT). Forty patients received comprehensive head and neck radiation including bilateral cervical nodal radiation, given with or without chemotherapy, for tumors of the nasopharynx, nasal cavity or paranasal sinuses, any T stage, N0-2. Fourteen received comprehensive treatment with proton therapy, and 26 were treated with IMRT, either comprehensively or matched to proton therapy delivered to the primary tumor site. Toxicity endpoints assessed included g-tube dependence at the completion of radiation and at 3 months after radiation, opioid pain medication requirement compared to pretreatment normalized as equivalent morphine dose (EMD) at completion of treatment, and at 1 and 3 months after radiation. In a multivariable model including confounding variables of concurrent chemotherapy and involved nodal disease, comprehensive head and neck radiation therapy using proton therapy was associated with a lower opioid pain requirement at the completion of radiation and a lower rate of gastrostomy tube dependence by the completion of radiation therapy and at 3 months after radiation compared to IMRT. Proton therapy was associated with statistically significant lower mean doses to the oral cavity, esophagus, larynx, and parotid glands. In subgroup analysis of 32 patients receiving concurrent chemotherapy, there was a statistically significant correlation with a greater opioid pain medication requirement at the completion of radiation and both increasing mean dose to the oral cavity and to the esophagus. Proton therapy was associated with significantly reduced radiation dose to assessed non-target normal tissues and a reduced rate of gastrostomy tube dependence and opioid pain medication requirements. This warrants further evaluation in larger studies, ideally with patient-reported toxicity outcomes and quality of life endpoints