High-risk clinical stage I nonseminomatous germ cell tumors: the case for chemotherapy

Testis cancer is the most frequent solid malignancy in young men. The majority of patients present with clinical stage I disease and about 50% of them are nonseminomatous germ cell tumors. In this initial stage of disease there is a subgroup of patients at high risk with a likelihood of more than 50% for relapse. Treatment options for these patients include: retroperitoneal lymph node dissection (RPLND), albeit 6-10% of patients will relapse outside the field of RPLND, active surveillance with even higher relapse rates and adjuvant chemotherapy. As most of these patients have the chance to become long-term survivors, avoidance of long-term side effects is of utmost importance. This review provides information on the potential of chemotherapy to achieve a higher chance of cure for patients with high-risk clinical stage I disease than its therapeutic alternatives and addresses toxicity and dose dependenc

The role of lymphadenectomy in high risk prostate cancer

Historically, patients with high risk prostate cancer were considered poor candidates for radical prostatectomy (RP) due to the likelihood of positive pelvic lymph nodes and decreased long term survival. Although there is still no consensus on the optimal therapy for this group of patients, there is increasing evidence that surgery could play a role. Cancer specific survival (CSS) rates after RP for locally advanced disease at 10year follow up range from 29 to 72%, depending on tumor differentiation. The role of pelvic lymph node dissection (PLND) in prostate cancer remains a controversial topic. Nonetheless, in conjunction with RRP extended PLND (ePLND) should be performed as extended lymph node dissection in lieu of standard PLND may increase staging accuracy, influence decision making with respect to adjuvant therapy and possibly impact outcome. High risk patients with organ confined prostate cancer and low volume (micro)metastatic disease may be the ones to profit most from this approac

Locoregional Failure Analysis in Head-and-Neck Cancer Patients Treated with IMRT

Purpose:: Purpose: Analysis of locoregional failure in head-and-neck cancer (HNC) following intensity-modulated radiation therapy (IMRT), with focus on the location of locoregional failures in relation to the chosen planning target volumes (PTVs) and dose distributions. Patients and Methods:: Between January 2002 and May 2006, 280 HNC patients were subjected to IMRT at the authors' institution. Mean follow-up was 23.2 months (3-59.3 months). Definitive IMRT was performed in 75% of all patients. In 71%, simultaneous cisplatin-based chemotherapy was given. 70% of patients presented with T3/4, T1-2 N2c/3 or recurred disease. Locoregional failure patterns were analyzed. Results:: 2-year local, nodal, distant, disease-free, and overall survival rates were 80%, 87%, 87%, 73%, and 82%, respectively. 46 local (16%) and 31 nodal (11%) failures have been observed so far. Local tumor persistence was seen in 23/46 cases (50%), and nodal persistence in 12/31 (39%), respectively. One marginal local failure developed in a patient referred for a recurred oral cavity tumor. Three nodal failures developed outside the PTVs at unexpected locations. All other failures have been confirmed "in field”. No failure occurred in level Ib or upper level II. Local failure occurred mainly following definitive IMRT for large tumors, nodal failure only in nodally positive patients with nodal high-risk features. Conclusion:: The dose-volume concept as used here has shown to be adequate, with disease failure developing at the site of the initial gross tumor manifestation inside the boost volum

Role of lymphadenectomy in clinically organ-confined prostate cancer

There has been considerable debate about the utility of pelvic lymph node dissection (PLND) when performing a radical prostatectomy. Reported practices vary from those who always perform an extended PLND to those who employ a predictive nomogram in their decision making to those who are increasingly not performing a PLND in low-risk disease. A Medline search was used to identify relevant manuscripts dealing with the role of lymphadenectomy in clinically organ-confined prostate cancer. A greater number of lymph nodes (LN) removed and examined at prostatectomy for prostate cancer appears to increase the likelihood of finding LN metastases and increase prostate cancer-specific survival even in patients who have histologically uninvolved LN. This survival benefit may result from more accurate staging and possible removal of occult metastases. The need for and extent of PLND in prostate cancer, especially in low-risk disease, however, is unlikel

IMRT in Hypopharyngeal Tumors

Background and Purpose:: Intensity-modulated radiation therapy (IMRT) data on hypopharyngeal cancer (HC) are scant. In this study, the authors report on early results in an own HC patient cohort treated with IMRT. A more favorable outcome as compared to historical data on conventional radiation techniques was expected. Patients and Methods:: 29 consecutive HC patients were treated with simultaneous integrated boost (SIB) IMRT between 01/2002 and 07/2005 (mean follow-up 16 months, range 4-44 months). Doses of 60-71 Gy with 2.0-2.2 Gy/fraction were applied. 26/29 patients were definitively irradiated, 86% received simultaneous cisplatin-based chemotherapy. 60% presented with locally advanced disease (T3/4 Nx, Tx N2c/3). Mean primary tumor volume measured 36.2 cm3 (4-170 cm3), mean nodal volume 16.6 cm3 (0-97 cm3). Results:: 2-year actuarial local, nodal, distant control, and overall disease-free survival were 90%, 93%, 93%, and 90%, respectively. In 2/4 patients with persistent disease (nodal in one, primary in three), salvage surgery was performed. The mean dose to the spinal cord (extension of > 5-15 mm) was 26 Gy (12-38 Gy); the mean maximum (point) dose was 44.4 Gy (26-58.9 Gy). One grade (G) 3 dysphagia and two G4 reactions (laryngeal fibrosis, dysphagia), both following the schedule with 2.2 Gy per fraction, have been observed so far. Larynx preservation was achieved in 25/26 of the definitively irradiated patients (one underwent a salvage laryngectomy); 23 had no or minimal dysphagia (G0-1). Conclusion:: Excellent early disease control and high patient satisfaction with swallowing function in HC following SIB IMRT were observed; these results need to be confirmed based on a longer follow-up period. In order to avoid G4 reactions, SIB doses of < 2.2 Gy/fraction are recommended for large tumors involving laryngeal structure

Nuclear Emulsion Film Detectors for Proton Radiography: Design and Test of the First Prototype

Proton therapy is nowadays becoming a wide spread clinical practice in cancer therapy and sophisticated treatment planning systems are routinely used to exploit at best the ballistic properties of charged particles. The information on the quality of the beams and the range of the protons is a key issue for the optimization of the treatment. For this purpose, proton radiography can be used in proton therapy to obtain direct information on the range of the protons, on the average density of the tissues for treatment planning optimization and to perform imaging with negligible dose to the patient. We propose an innovative method based on nuclear emulsion film detectors for proton radiography, a technique in which images are obtained by measuring the position and the residual range of protons passing through the patient's body. Nuclear emulsion films interleaved with tissue equivalent absorbers can be fruitfully used to reconstruct proton tracks with very high precision. The first prototype of a nuclear emulsion based detector has been conceived, constructed and tested with a therapeutic proton beam at PSI. The scanning of the emulsions has been performed at LHEP in Bern, where a fully automated microscopic scanning technology has been developed for the OPERA experiment on neutrino oscillations. After track reconstruction, the first promising experimental results have been obtained by imaging a simple phantom made of PMMA with a step of 1 cm. A second phantom with five 5 x 5 mm^2 section aluminum rods located at different distances and embedded in a PMMA structure has been also imaged. Further investigations are in progress to improve the resolution and to image more sophisticated phantoms.Comment: Presented at the 11th ICATPP Conference on Astroparticle, Particle, Space Physics, Detectors and Medical Physics Applications, Como (Italy), October 200

Osteoradionecrosis of the Mandible: Minimized Risk Profile Following Intensity-Modulated Radiation Therapy (IMRT)

Background and Purpose:: Osteoradionecrosis (ON) of the mandible is a serious late complication of high-dose radiation therapy for tumors of the oropharynx and oral cavity. After doses between 60 and 72 Gy using standard fractionation, an incidence of ON between 5% and 15% is reported in a review from 1989, whereas in more recent publications using moderately accelerated or hyperfractionated irradiation and doses between 69 and 81 Gy, the incidence of ON is between 60 Gy for oropharyngeal or oral cavity cancer). 21/73 patients were treated in a postoperative setting, 52 patients underwent primary definitive irradiation. In 56 patients concomitant cisplatin-based chemotherapy was applied. Mean follow-up time was 22 months (12-46 months). Oral cavity including the mandible bone outside the planning target volume was contoured and dose-volume constraints were defined in order to spare bone tissue. Dose-volume histograms were obtained from contoured mandible in each patient and were analyzed and related to clinical mandible bone tolerance. Results:: Using IMRT with doses between 60 and 75 Gy (mean 67 Gy), on average 7.8, 4.8, 0.9, and 0.3 cm3 were exposed to doses > 60, 65, 70, and 75 Gy, respectively. These values are substantially lower than when using three-dimensional conformal radiotherapy. The difference has been approximately quantified by comparison with a historic series. Additional ON risk factors of the patients were also analyzed. Only one grade 3 ON of the lingual horizontal branch, treated with lingual decortication, was observed. Conclusion:: Using IMRT, only very small partial volumes of the mandibular bone are exposed to high radiation doses. This is expected to translate into a further reduction of ON and improved osseointegration of dental implant

Caveats when interpreting intravenous urograms following ileal orthotopic bladder substitution

The aim of this study was to evaluate the appearance of the upper urinary tract following cystectomy and ileal orthotopic bladder substitution. Intravenous urograms (IVUs) performed preoperatively and at regular intervals postoperatively on 87 long-term survivors (minimum survival, 5 years) following ileal orthotopic bladder substitution were reviewed. Distention of the collecting system with blunted or rounded fornices was defined as dilatation. If in addition contrast medium excretion was delayed on the 5-min film, this was defined as obstruction. Collecting system dilatation was present on all IVU films obtained from most patients (80%) within 6 months of surgery, even in the absence of urinary tract obstruction. In contrast, dilatation was commonly seen only on the 20-min postinjection films (79%) on urograms performed more than 1 year following surgery, but not encountered on the other two postinjection radiographs (at 5 and 60min). Five years after surgery, permanent obstruction was observed in only five (3%) renoureteral units. Dilatation of the upper urinary tract after ileal orthotopic bladder substitution is a frequent finding on the 5-min, 20-min, and 60-min films during the early postoperative period but is found only on the 20-min film 1 year and later after surgery. These findings should not be overinterpreted as obstructio

Interactive Effects of N-, P- and K-Nutrition and Drought Stress on the Development of Maize Seedlings

Global climate change is likely to increase the risk of frequent drought. Maize, as the principal global cereal, is particularly impacted by drought. Nutrient supply may improve plant drought tolerance for better plant establishment during seedling growth stages. Thus, this study investigated the interactive effects of drought and the application of the nutrients N, P and K either individually or in combination. The maize seedlings were harvested between 12 and 20 days after sowing, and the leaf area, shoot fresh and dry weight and root dry weight were determined, and shoot water content and root/shoot dry weight ratio were calculated. Among the N, P and K fertilization treatments applied individually or in combination, the results showed that there was generally a positive effect of combined NPK and/or NP nutrient supply on shoot growth such as leaf area, shoot fresh and dry weight at day 20 after sowing under both well-watered and drought conditions compared with no nutrient supply. Compared with the effect of N and P nutrient supply, it seems that K was not limiting to plant growth due to the mineralogical characteristics of the illitic-chloritic silt loam used, which provided sufficient K, even though soil tests showed a low K nutrient status. Interestingly, the root/shoot ratio remained high and constant under drought regardless of NPK application, while it decreased with NPK applications in the well-watered treatment. This suggests that the higher root/shoot ratios with N, NP, PK and NPK under drought could be exploited as a strategy for stress tolerance in crop plants

Locoregional failure analysis in head-and-neck cancer patients treated with IMRT

PURPOSE: Analysis of locoregional failure in head-and-neck cancer (HNC) following intensity-modulated radiation therapy (IMRT), with focus on the location of locoregional failures in relation to the chosen planning target volumes (PTVs) and dose distributions. PATIENTS AND METHODS: Between January 2002 and May 2006, 280 HNC patients were subjected to IMRT at the authors' institution. Mean follow-up was 23.2 months (3-59.3 months). Definitive IMRT was performed in 75% of all patients. In 71%, simultaneous cisplatin-based chemotherapy was given. 70% of patients presented with T3/4, T1-2 N2c/3 or recurred disease. Locoregional failure patterns were analyzed. RESULTS: 2-year local, nodal, distant, disease-free, and overall survival rates were 80%, 87%, 87%, 73%, and 82%, respectively. 46 local (16%) and 31 nodal (11%) failures have been observed so far. Local tumor persistence was seen in 23/46 cases (50%), and nodal persistence in 12/31 (39%), respectively. One marginal local failure developed in a patient referred for a recurred oral cavity tumor. Three nodal failures developed outside the PTVs at unexpected locations. All other failures have been confirmed "in field". No failure occurred in level Ib or upper level II. Local failure occurred mainly following definitive IMRT for large tumors, nodal failure only in nodally positive patients with nodal high-risk features. CONCLUSION: The dose-volume concept as used here has shown to be adequate, with disease failure developing at the site of the initial gross tumor manifestation inside the boost volume