11C-Choline PET/CT in the primary diagnosis of prostate cancer: impact on treatment planning.

AIM: Aim of the present study was to evaluate the usefulness of 11C-choline PET/CT for detecting lymphatic or haematogenous spread and for planning radiotherapy in patients with medium-to-high risk prostate cancer. METHODS: We have included 61 consecutive patients recently diagnosed with cancer prostate by biopsy. All patients were classified as medium-to-high risk: Gleason: 7-9; PSA: 6.3-30.4 ng/mL; stage T2c (N.=20) or stage T3 (N.=41). Image acquisition began 5 min after intravenous injection of 11C-choline (656+119 MBq), starting at the pelvis and continuing craniocaudally. Images were interpreted visually to evaluate uptake by the prostate gland. Lymph nodes with 11C-choline uptake were considered invaded, regardless of their size. Bone lesions were considered positive when they showed greater focal uptake than the surrounding bone. In patients with evidence of lymph-node invasion or bone metastases (15 patients), disease was classified as locoregional, oligometastatic, or multimetastatic. RESULTS: All patients had prostate gland uptake (20 focal, 8 bifocal, and 33 multifocal). Extraprostatic disease was present in 15 patients (24.6%), as follows: 9 (60%) in a single location: in an infradiaphragmatic lymph node (N.=6), in a supradiaphragmatic lymph node (N.=1), and in bone (M1) (N.=2). Six (40%) as multifocal invasion: with both infra- and supradiaphragmatic lymph node involvement (N.=2); with infradiaphragmatic lymph node involvement and M1 bone metastases (N.=3); and infra- and supradiaphragmatic lymph node involvement plus M1 bone metastases (N.=1). Disease was classified as locoregional (N.=6), oligometastatic (N.=5), and multimetastatic (N.=4). The 11 (73.3%) patients with locoregional and oligometastatic disease were selected to undergo intensity-modulated radiation therapy with dose escalation based on the PET findings. CONCLUSION: Our results suggest that 11C-choline PET/CT is a useful one-stop diagnostic procedure for evaluating patients with medium/high risk prostate cancer scheduled for radical treatment. 11C-choline PET/CT can reliably rule out lymph node involvement and remote metastases, allowing to select candidates for radiotherapy and to plan their treatment.

[Prostate cancer and androgen deprivation: benefits of psychological counseling]. / Cancer de la prostate et déprivation androgénique: bénéfices d'un accompagnement psychologique.

Androgen deprivation is a therapeutic option for patients with prostate cancer, however with a range of side effects that negatively affects their physical and psychological condition. A multidisciplinary care program, ADAPP ("Androgenic deprivation in prostate cancer patients"), has been created with a special focus on managing these side effects. This article describes the intervention of the liaison psychiatry within this program, with care options ranging from psychological support to intensive psychotherapy to address patients' intrapsychic dynamics throughout this care program. Clinical cases are reported to illustrate the relevance and the necessity of this specialized counselling.

Excess of cardiovascular mortality among node-negative breast cancer patients irradiated for inner-quadrant tumors.

BACKGROUND: Radiotherapy of the left breast is associated with higher cardiovascular mortality linked to cardiotoxic effect of irradiation. Radiotherapy of inner quadrants can be associated with greater heart irradiation, but no study has evaluated the effect of inner-quadrant irradiation on cardiovascular mortality. PATIENTS AND METHODS: We identified 1245 women, the majority with breast-conserving surgery, irradiated for primary node-negative breast cancer from 1980 to 2004 registered at the Geneva Cancer Registry. We compared breast cancer-specific and cardiovascular mortality between inner-quadrant (n = 393) versus outer-quadrant tumors (n = 852) by multivariate Cox regression analysis. RESULTS: After a mean follow-up of 7.7 years, 28 women died of cardiovascular disease and 91 of breast cancer. Patients with inner-quadrant tumors had a more than doubled risk of cardiovascular mortality compared with patients with outer-quadrant tumors (adjusted hazard ratio 2.5; 95% confidence interval 1.1-5.4). Risk was particularly increased in the period with higher boost irradiation. Patients with left-sided breast cancer had no excess of cardiovascular mortality compared with patients with right-sided tumors. CONCLUSIONS: Radiotherapy of inner-quadrant breast cancer is associated with an important increase of cardiovascular mortality, a possible result of higher irradiation of the heart. For patients with inner-quadrant tumors, the heart should be radioprotected.

Three-phase 18F-fluorocholine PET/CT in the evaluation of prostate cancer recurrence.

AIM: Contribution of 3-phase 18F-fluorocholine PET/CT in suspected prostate cancer recurrence at early rise of PSA. PATIENTS, METHODS: Retrospective analysis was performed in 47 patients after initial treatment with radiotherapy (n=30) or surgery (n=17). Following CT, 10 minutes list-mode PET acquisition was done over the prostate bed after injection of 300 MBq of 18F-fluorocholine. Three timeframes of 3 minutes each were reconstructed for analysis. All patients underwent subsequent whole body PET/CT. Delayed pelvic PET/CT was obtained in 36 patients. PET/CT was interpreted visually by two observers and SUVmax determined for suspicious lesions. Biopsies were obtained from 13 patients. RESULTS: Biopsies confirmed the presence of cancer in 11 of 13 patients with positive PET for a total of 15 local recurrences in which average SUVmax increased during 14 minutes post injection and marginally decreased in delayed scanning. Conversely inguinal lymph nodes with mild to moderate metabolic activity on PET showed a clearly different pattern with decreasing SUVmax on dynamic images. Three-phase PET/CT contributed to the diagnostic assessment of 10 of 47 patients with biological evidence of recurrence of cancer. It notably allowed the discrimination of confounding blood pool or urinary activity from suspicious hyperactivities. PET/CT was positive in all patients with PSA>or=2 ng/ml (n=34) and in 4/13 patients presenting PSA values<2 ng/ml. CONCLUSION: 18F-fluorocholine 3-phase PET/CT showed a progressively increasing SUVmax in biopsy confirmed cancer lesions up to 14 minutes post injection while decreasing in inguinal lymph nodes interpreted as benign. Furthermore, it was very useful in differentiating local recurrences from confounding blood pool and urinary activity.

Characteristics and outcome of prostate cancer with PSA <4 ng/ml at diagnosis: a population-based study.

This population-based study aims to assess prognosis of prostate cancer diagnosed with prostate-specific antigen (PSA) levels <4 ng/ml in routine care. Materials and methods We compared prostate cancer patients with low PSA values (n=59) with other prostate cancer patients (n=1330) by logistic regression and the Cox model using data from the Geneva Cancer Registry. Results Patients with low PSA values more frequently had early-stage and well differentiated tumours. Nevertheless, 35% presented with aggressive tumour characteristics or metastases. After adjustment for other prognostic factors, prostate cancer-specific mortality was similar for both groups (hazard ratio: 1.1; 95%CI: 0.6-2.2). Conclusion We conclude that cancer with low PSA values at diagnosis is not indolent.

[From bunker construction to patient treatment: quality controls applied to modern radiotherapy techniques]. / De la construction du bunker à la prise en charge du patient : contrôles qualité des techniques modernes de radiothérapie.

Installation and use of a new radiotherapy device require an adequate quality and safety policy. The process leading to the commissioning of an accelerator following the construction of a bunker includes, among other tasks, the installation of the accelerator, the verification of compliance with the specifications, the signature of the acceptance specification as well as the process of characterization and modeling of the accelerator before its clinical use. The emergence of modern radiotherapy techniques, such as intensity modulated conformational radiotherapy and stereotactic radiotherapy, has resulted in more complex quality controls. The purpose of this article is to explain the different stages of the implementation of innovative radiotherapy techniques and to specify their features.

Contouring workload in adjuvant breast cancer radiotherapy.

PURPOSE: To measure the impact of contouring on worktime in the adjuvant radiation treatment of breast cancer, and to identify factors that might affect the measurements. MATERIAL AND METHODS: The dates and times of contouring clinical target volumes and organs at risk were recorded by a senior and by two junior radiation oncologists. Outcome measurements were contour times and the time from start to approval. The factors evaluated were patient age, type of surgery, radiation targets and setup, operator, planning station, part of the day and day of the week on which the contouring started. The Welch test was used to comparatively assess the measurements. RESULTS: Two hundred and three cases were included in the analysis. The mean contour time per patient was 34minutes for a mean of 4.72 structures, with a mean of 7.1minutes per structure. The clinical target volume and organs at risk times did not differ significantly. The mean time from start to approval per patient was 29.4hours. Factors significantly associated with longer contour times were breast-conserving surgery (P=0.026), prone setup (P=0.002), junior operator (P<0.0001), Pinnacle planning station (P=0.026), contouring start in the morning (P=0.001), and contouring start by the end of the week (P<0.0001). Factors significantly associated with time from start to approval were age (P=0.038), junior operator (P<0.0001), planning station (P=0.016), and contouring start by the end of the week (P=0.004). CONCLUSION: Contouring is a time-consuming process. Each delineated structure influences worktime, and many factors may be targeted for optimization of the workflow. These preliminary data will serve as basis for future prospective studies to determine how to establish a cost-effective solution.

Early-stage Favourable Anal Cancer: A Retrospective Analysis of Clinical Outcomes of a Moderately Low Dose Elective Nodal Intensity-modulated Radiotherapy Schedule.

In this retrospective study we evaluated the long-term results of 35 early-stage favourable T1-2 N0 M0 anal cancer patients treated with intensity-modulated radiotherapy techniques combining low dose prophylactic inguinal-pelvic irradiation with dose-escalated boost. Optimal locoregional control and good tolerance makes this treatment a valuable alternative to brachytherapy boost and involved-field radiotherapy plans.

Pattern of Progression after Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Nodal Recurrences.

AIMS: To report the relapse pattern of stereotactic body radiotherapy (SBRT) for oligorecurrent nodal prostate cancer (PCa). MATERIALS AND METHODS: PCa patients with ≤3 lymph nodes (N1/M1a) at the time of recurrence were treated with SBRT. SBRT was defined as a radiotherapy dose of at least 5 Gy per fraction to a biological effective dose of at least 80 Gy to all metastatic sites. Distant progression-free survival was defined as the time interval between the first day of SBRT and appearance of new metastatic lesions, outside the high-dose region. Relapses after SBRT were recorded and compared with the initially treated site. Secondary end points were local control, time to palliative androgen deprivation therapy and toxicity scored using the Common Terminology Criteria for Adverse Events v4.0. RESULTS: Overall, 89 metastases were treated in 72 patients. The median distant progression-free survival was 21 months (95% confidence interval 16-25 months) with 88% of patients having ≤3 metastases at the time of progression. The median time from first SBRT to the start of palliative androgen deprivation therapy was 44 months (95% confidence interval 17-70 months). Most relapses (68%) occurred in nodal regions. Relapses after pelvic nodal SBRT (n = 36) were located in the pelvis (n = 14), retroperitoneum (n = 1), pelvis and retroperitoneum (n = 8) or in non-nodal regions (n = 13). Relapses after SBRT for extrapelvic nodes (n = 5) were located in the pelvis (n = 1) or the pelvis and retroperitoneum (n = 4). Late grade 1 and 2 toxicity was observed in 17% (n = 12) and 4% of patients (n = 3). CONCLUSION: SBRT for oligometastatic PCa nodal recurrences is safe. Most subsequent relapses are again nodal and oligometastatic.

Prospective pilot study of sildenafil for treatment of postradiotherapy erectile dysfunction in patients with prostate cancer.

PURPOSE: Erectile dysfunction is a common late complication patients may experience after external-beam radiotherapy for prostate cancer. The efficacy and safety of oral sildenafil to correct sexual dysfunction caused by external-beam radiotherapy was studied in patients participating in our prospective trial. PATIENTS AND METHODS: Thirty-five assessable patients participated in this prospective pilot study. Using a 25-point scale based on the International Index of Sexual Function, erectile dysfunction was assessed weekly, during which time patients received sildenafil 100 mg orally once a week for 6 consecutive weeks. Response was defined as a score of 18 or more, corresponding to at least one successful attempt at sexual intercourse per week. RESULTS: Thirty patients (86%) completed the 6-week study. Seventy-seven percent of these patients had significantly improved erectile function, allowing recovery of full capacity for sexual intercourse. Of 27 patients not receiving concomitant hormone treatment, failure to respond was observed in only four patients (15%) compared with four (50%) of eight patients receiving hormonal treatment during the study. The time course of response was gradual, with 40%, 57%, 66%, 69%, and 74% responding at weeks 1 through 5, respectively. Therapy was generally well tolerated. The most frequently reported side effects in patients were flushing (37%), transient headache (17%), and dyspepsia (9%). No patient reported priapism, and no cardiovascular event or death was observed. After response, 12 patients (34%) reported the ability to achieve and maintain an erection sufficient for intercourse in the absence of sildenafil (ie, 24 hours to 6 days after taking the medication). CONCLUSION: This study suggests that oral sildenafil is well tolerated and can reverse erectile dysfunction after radiotherapy in a substantial proportion of prostate cancer patients.

Phase II trial of up-front accelerated thoracic radiotherapy combined with chemotherapy and optional up-front prophylactic cranial irradiation in limited small-cell lung cancer. Groupe d'Oncologie Thoracique des Régions Alpines.

PURPOSE: To investigate the feasibility and outcome of bifractionated, up-front thoracic radiotherapy (TR) (45 Gy in 30 fractions of 1.5 Gy twice daily over 3 weeks) combined with chemotherapy (CT) (six cycles of cisplatin and etoposide) and optional low-dose, up-front prophylactic cranial irradiation (18 Gy in 10 fractions of 1.8 Gy twice daily over 5 days) in limited small-cell lung cancer. PATIENTS AND METHODS: CT (etoposide 100 mg/m(2) for 3 days and cisplatin 25 mg/m(2) for 3 days) was started on day 8 or 15 after the first TR treatment. In the five subsequent cycles, cisplatin was given as a single 100-mg/m(2) dose on day 1 every 4 weeks. A total of 52 patients were entered (41 men and 11 women); the median age was 55 years (range, 33 to 67 years). World Health Organization performance status was 0 in 34 patients, 1 in 16 patients, and 2 in two patients. Thirty-six patients (69%) received the full planned six cycles of CT. RESULTS: All treated patients were assessable for response. Thirty-one patients (60%) achieved a complete response, and 16 (30%) had a partial response. One-, 3-, and 4-year survival rates were 74% (95% confidence interval [CI], 60% to 84%), 34% (95% CI, 21% to 49%), and 32% (95 CI, 16% to 46%), respectively. The median survival time was 18 months. Event-free survival at 1 year was 45% (95% CI, 32% to 58%) and at 3 years, 30% (95% CI, 18% to 44%). The main radiation-related acute toxicity was esophageal: 38% of the patients experienced grade 3 or 4 acute toxicity. CT was well tolerated. Although grade 3/4 neutropenia was observed in 86% of the patients, only 4% presented with associated fever. Grade 3/4 nausea and vomiting was seen in 35% of patients. CONCLUSION: This trial demonstrates that up-front accelerated TR associated with CT is feasible, has acceptable toxicity, and shows considerable long-term survival potential.

Accelerated radiotherapy, carbogen, and nicotinamide in glioblastoma multiforme: report of European Organization for Research and Treatment of Cancer trial 22933.

PURPOSE: A three-step phase I/II trial associating accelerated radiotherapy with carbogen (step 1, ARCO), with nicotinamide (step 2, ARN), or with both (step 3, ARCON) was conducted, the aim of which was to overcome the effects of proliferation and hypoxia as potential causes of tumor radioresistance in glioblastoma multiforme. PATIENTS AND METHODS: Radiotherapy consisted of 60 Gy delivered over 4 weeks in 1.5-Gy fractions twice daily, 5 days a week. Carbogen breathing was started 5 minutes before each fraction and continued until the end of each treatment session. Nicotinamide was given daily as a single oral dose of 85 mg/kg. RESULTS: A total of 115 patients with a median age of 55 years were registered. Of 107 eligible patients, 23 were registered in step 1, 28 in step 2, and 56 in step 3. The planned treatment was administered without any interruption in 72% of patients (86% in ARCO but 68% in ARN and ARCON). The incidence and severity of acute skin and mucous membrane toxicity were higher in patients who received nicotinamide (ie, the ARN and ARCON groups). Grade 1 to 2 gastrointestinal toxicity was observed in 44% of patients in the ARN group and 32% of patients in the ARCON group, but only in 8% of patients in the ARCO group. Eight percent of evaluated patients presented with abnormal liver test results at treatment completion. The dose of corticosteroids had to be increased in 44% of patients. Late neurologic side effects were similar in all treatment steps and were observed mostly in patients with disease progression. Median survival times for patients treated with ARCO, ARN, and ARCON were 10.1, 9.7, and 11.1 months, respectively. CONCLUSION: Feasibility of ARCO treatment was good but that of ARN and ARCON was only fair. This probably reflected the higher acute toxicity rate, particularly gastrointestinal, for patients receiving nicotinamide. The dose of corticosteroids had to be increased frequently during treatment, suggesting a higher than expected acute neurologic toxicity. Overall survival was similar in the three treatment steps and not different when compared with results of other series that used radiotherapy alone.

Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease.

PURPOSE: To evaluate retrospectively the cumulative risk probability and factors correlated with renal dysfunction after allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From October 1984 to July 1994, 84 patients with malignant hematopoietic diseases received allogeneic BMT after conditioning with high-dose chemotherapy and total-body irradiation (TBI). Seventy-nine patients with normal renal function before conditioning are included in this study. Conditioning included high-dose cyclophosphamide without (n = 46) or with (n = 33) other agents (daunorubicin, busulfan, cytarabine, and thiotepa) followed by TBI. The TBI dose prescribed to the center of the abdomen was 10 Gy for 24 patients, 12 Gy for 32, and 13.5 Gy for 23. In vitro T-cell depletion was undertaken in 48 cases. The post-BMT nephrotoxicity of aminoglycosides, vancomycin, amphotericin, and cyclosporine was assessed. Time to renal dysfunction was defined as the time to a persistent increase of serum creatinine (SCr) level greater than 110 mumol/L. The potential influence of sex, age, diagnosis, chimerism, and graft-versus-host disease (GvHD) on renal dysfunction was also assessed. RESULTS: The 18-month probability of renal dysfunction-free survival (RDFS) for the whole group was 77%. Only TBI dose and presence of GvHD were significantly correlated with renal dysfunction by multivariate analysis. The 18-month probabilities of RDFS were 95%, 74%, and 55% for the patients conditioned with 10, 12, and 13.5 Gy, respectively. The 18-month RDFS probabilities were 88% and 61% for patients without and with GvHD, respectively. Combining both variables, we have defined two risk categories: low-risk (ie, 10 Gy TBI with/without GvHD and 12 Gy TBI without GvHD) and high-risk (ie, 12 Gy TBI with GvHD and 13.5 Gy TBI with/without GvHD). The predicted 18-month RDFS rates were 93% and 52% for the low- and high-risk groups, respectively. CONCLUSION: Renal dysfunction after allogeneic BMT is strongly related to the delivered TBI dose (and dose per fraction) and to the presence of GvHD. Renal shielding should be recommended if a TBI dose greater than 12 Gy (fractionated twice daily over 3 days) is to be prescribed. Furthermore, in those cases with a high risk of developing GvHD (eg, unrelated allogeneic BMT, absence of T-cell depletion), these data suggest that kidney doses greater than 10 Gy should be avoided.

Longitudinal follow-up of body composition in hematopoietic stem cell transplant patients.

Patients with hematological malignancies are well nourished prior to allogeneic hematopoietic stem cell transplantation (HSCT). HSCT and associated complications can affect body composition. The study evaluated cross-sectionally the prevalence and longitudinally the changes in lean body mass index (LBMI) in HSCT patients. Patients (n=82) were classified as normal or low LBMI. Logistic regression analyses were used to estimate odds ratios (OR) for low vs normal LBMI, between healthy volunteers and patients; for limited or extensive vs no chronic graft-versus-host-disease (GVHD); and for decreased (Karnofsky <80) vs normal functional status (>80). Patients were significantly more likely to have low LBMI at 6, 12 months, 2-3, 4-6 and >6 years than volunteers. In all, 38% of patients were below pre-HSCT LBMI at 4-6 years post-HSCT. Low LBMI was significantly associated with steroid treatment (OR 2.6, confidence intervals (CI) 1.3-5.2, P=0.008); limited (OR 5.5, CI 1.7-18.5, P=0.005) or extensive chronic GVHD (OR 20.3, CI 5.7-71.6, P<0.001); and decreased performance status (Karnofsky scores of < or =80) (OR 2.7, CI 1.3-5.9, P=0.01). Patients were more likely to have low LBMI than volunteers. Chronic GVHD and low performance status were associated with low LBMI; thus, complications and/or treatment increase the likelihood of low LBMI.

Significance of 18F-fluorocholine PET/CT positive pulmonary lesions in prostate cancer patients.

AIM: To assess the frequency and the significance of incidental pulmonary lesions with 18F-fluorocholine (18F-FCH) PET/CT in prostate cancer (PCa) patients. PATIENTS, METHODS: 225 consecutive PCa patients referred for 18F-FCH PET/CT (median age 68 years) were retrospectively evaluated for the presence of lesions in the lungs: 173 referred for restaging and 52 for initial staging regarding their high risk of extra prostatic extension. The final diagnosis was based on histopathological or on clinical and radiological follow-up. RESULTS: 13 patients had 18F-FCH positive pulmonary and 8 patients malignant lesions: 5 patients (38%) had a primary lung cancer (2 squamous cell carcinomas, 1 papillary adenocarcinoma, 1 typical pulmonary carcinoid, 1 bronchioloalveolar carcinoma) and 3 patients (23%) PCa metastases. Benign lesions were found in 5 subjects (38%). SUVmax and maximum diameter were neither significantly different in primary and metastatic tumors nor between malignant and benign lesions. CONCLUSIONS: Although our results suggest that incidental uptake in the lungs in PCa patients are nonspecific, their detection may have a significant impact on patient management knowing that more than 60% represent malignant disease.

Nausea and vomiting in fractionated radiotherapy: a prospective on-demand trial of tropisetron rescue for non-responders to metoclopramide.

A prospective trial was performed to better assess the risk of nausea and vomiting and the rescue value of tropisetron (TRO), a 5-HT3 receptor antagonist, in 88 patients undergoing fractionated radiotherapy to the abdomen or to large supradiaphragmatic fields and failing a first anti-emetic trial with metoclopramide (MET). Nausea was graded 0 (absent), 1 (mild), 2 (moderate) and 3 (severe). Nausea requiring anti-emetics (> or = grade 2) was present in 64% of the patients. MET was able to control nausea (< or = grade 1) in 26 of 58 patients (45%) who developed > or = grade 2 nausea during radiation treatment (2 patients vomiting without nausea included). 34 patients required TRO, and 31 experienced immediate relief. However, nausea (> or = grade 2) recurred in 7 patients from 1 to 3 weeks after starting TRO. Sex, age, field type and field size (cm2) did not influence the incidence and severity of nausea and vomiting. Only 24/88 patients vomited after starting radiotherapy. MET helped to eliminate emesis in one third of these patients. TRO helped to control vomiting in 73% of the salvaged patients. Constipation was observed in 8 patients on TRO and was a reason to stop the medication in 4 cases.

Potential improvement of three dimension treatment planning and proton beams in fractionated radiotherapy of large cerebral arteriovenous malformations.

The treatment of large cerebral arteriovenous malformations is a surgical challenge, especially for deep seated brain locations. Furthermore, these lesions are unfit for radiosurgical approaches due to a high risk of complications secondary to high radiation doses to large brain volumes. Fractionated precision radiotherapy can potentially deliver high, uniform, target-contoured dose distributions optimizing the dose reduction to the critical surrounding brain. The results of a study are presented in such a way that dose distributions achievable with proton beams are compared to those with 10 MV x-rays; and the potential improvements with protons evaluated, relying heavily on dose-volume histograms to examine the coverage of the lesion as well as the dose to the normal brain, brain-stem, and optic chiasm.

Potential impact of improvements in radiation therapy on quality of life and survival.

The NCI goal for the U.S. is to reduce the cancer mortality rate to one-half by the year 2000. Part of this improvement will be due to use of state of art treatment on a population wide basis and in addition, major improvements in efficacy of treatment. More effective radiation therapy will result in fewer local failures, increased survival, reduced treatment associated morbidity, and less frequent complications of treatment. The latter two aspects are very important to quality of life. If radiation combined with other modalities (e.g., sensitizers) were to become of greatly enhanced efficacy, then the number of patients requiring cystectomy, abdominal perineal resection, pneumonectomy, amputation, etc., would come down. The beneficial consequence would be fewer patients subjected to permanent ileostomy, colostomy, etc. The increase in survival if local failure were eliminated was estimated to be the decrease in local failure less the same loss in the new local controls due to DM as obtained in the local control patients after conventional treatment. For all sites, patients experience higher survival rates if they do not have local failure. For those sites where loss due to metastasis is not high, more effective local therapy would result in numerically impressive gains in survival.

Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation.

PURPOSE: Conventional postoperative photon-beam radiotherapy to the spine in children with medulloblastoma/PNET is associated with severe late effects. This morbidity (growth and developmental) is related to the exit dose of the beams and is particularly severe in young children. With the purpose of reducing this toxicity, a dosimetric study was undertaken in which proton therapy was compared to standard megavoltage photon treatment. METHODS AND MATERIALS: The results of a comparative dosimetric study are presented in such a way that the dose distribution achievable with a posterior modulated 100 MeV proton beam (spot scanning method) is compared with that of a standard set of posterior 6 MV x-ray fields. The potential improvements with protons are evaluated, using dose-volume histograms to examine the coverage of the target as well as the dose to the vertebral bodies (growth plates), lungs, heart, and liver. RESULTS: The target (i.e., the spinal dural sac) received the full prescribed dose in both treatment plans. However, the proportions of the vertebral body volume receiving > or = 50% of the prescribed dose were 100 and 20% for 6 MV x-rays and protons, respectively. For 6 MV x-rays > 60% of the dose prescribed to the target was delivered to 44% of the heart volume, while the proton beam was able to completely avoid the heart, the liver, and in all likelihood the thyroid and gonads as well. CONCLUSION: The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET. The potential bone marrow and growth arrest sparing effects make this approach specially attractive for intensive chemotherapy protocols and for very young children. Sparing the thyroid gland, the posterior heart wall, and the gonads may be additional advantages in assuring a long-term posttreatment morbidity-free survival.

Potential role of intensity modulated proton beams in prostate cancer radiotherapy.

PURPOSE: The present study was undertaken to assess the potential benefit of intensity modulated (IM) proton beams in optimizing the dose distribution to safely escalate the tumor dose in prostate cancer radiotherapy. METHODS AND MATERIALS: Four treatment plans were compared in a prostate cancer patient aiming to deliver 81 Gy to the target: 1) conformal 18 MV X-rays, 6-fields; 2) 214 MeV protons, 2-fields; 3) IM 15 MV X-rays, 5-fields; and 4) 177-200 Mev IM protons, 5-fields as in Plan 3. In addition, IM methods were used to further escalate the tumor dose to 99 Gy. Dose-volume histograms (DVH) were used to physically compare the treatment plans. DVH data were also used to obtain normal tissue complication probabilities (NTCP) for the rectum, bladder, femoral heads, and tumor control probabilities. RESULTS: Although the planning target volume dose distribution was satisfactory with the four treatment plans, the homogeneity was slightly reduced in both X-ray plans (IM and standard) and the low-to-medium doses delivered to all organs at risk, and other normal tissues were significantly reduced by both proton plans. For a prescribed dose of 81 Gy, only the IM X-ray and IM proton plans both succeeded in predicting an acceptably low NTCP for the rectum (<5%, Grade 3). The integral nontarget dose was significantly reduced with IM proton beams (i.e., 3.1, 1.3, and 1.7 times less than Plans 1, 2, and 3, respectively). When escalating the dose to 99 Gy, no additional improvement between IM protons and IM X-ray beams was observed. CONCLUSION: Both IM X-ray and proton beams were able to optimize the dose distribution and comply with the goal of delivering the highest dose to the target while reducing the risk of severe morbidity to acceptable levels. The main advantage compared to IM X-rays was that IM protons succeeded in significantly reducing the low-to-medium dose to the nontarget tissues and achieved a small improvement in planning target volume (PTV) dose heterogeneity.