Macroscopic locoregional relapse from prostate cancer: which role for salvage radiotherapy?

INTRODUCTION: Salvage radiotherapy (SRT) after radical prostatectomy for prostate cancer (PCa) is recommended as soon as PSA rises above 0.20 ng/ml, but many patients (pts) still experience local macroscopic relapse. The aim of this multicentric retrospective analysis was to evaluate the role of SRT in pts with macroscopic relapse. MATERIALS AND METHODS: From 2001 to 2016, 105 consecutive pts with macroscopic PCa relapse underwent SRT ± androgen deprivation therapy (ADT). Mean age was 72 years. At time of relapse, 29 pts had a PSA value < 1.0 ng/mL, 50 from 1.1 to 5, and 25 pts > 5. Before SRT, 23 pts had undergone 18F-choline PET and 15 pts pelvic MRI. Ninety-four pts had prostatic bed relapse only, and four nodal involvement. Fifty-one pts were previously submitted to first-line ADT, while 6 pts received ≥ 2 lines. RESULTS: At a median follow-up of 52 months, 89 pts were alive, while 16 were dead. Total RT dose to macroscopic lesions was > 70 Gy in 58 pts, 66-70 Gy in 43, and < 66 Gy in 4 pts. In 72 pts, target volume encompassed only the prostatic bed with sequential boost to macroscopic site; 33 pts received prophylactic pelvic RT. Ten-year overall survival was 76.1%, while distant metastasis-free survival was 73.3%. No grade 4-5 toxicities were found. CONCLUSIONS: SRT ± ADT for macroscopic relapse showed a favorable oncological outcome supporting its important role in this scenario. Data from this series suggest that SRT may either postpone ADT or improve results over ADT alone in appropriately selected pts.

The Role of Adjuvant Radiotherapy in the Treatment of Papillary Tumors of the Pineal Region: Some General Considerations and a Case Report.

BACKGROUND: Papillary tumor of the pineal region (PTPR) is a recently defined tumor entity. Its clinical course is characterized by frequent local recurrence, and patients may experience the burden of symptoms due to the anatomical location of the growing mass. Guidelines for treatment protocols, and the role of radiotherapy are still being investigated. CASE: We report the case of a 27-year old woman who was referred to our department after she was diagnosed with PTPR and had undergone multiple surgical interventions. We delivered adjuvant conformal radiotherapy on the gross residual tumor to a total dose of 59.4 Gy (33 × 1.8 Gy). DISCUSSION: After a follow-up period of 41 months, we obtained a complete response to the treatment, according to the Response evaluation criteria in solid tumors criteria (RECIST). Radiation treatment was well tolerated, and the patient did not develop acute and late side effects. The neurological symptoms, which were documented at the diagnosis and after the surgical procedure, have not been recorded at last follow-up. CONCLUSIONS: Formal consensus for managing patients with a diagnosis of PTPR are nonexistent. Despite surgery, this tumor has a tendency to recur. Radiotherapy could have a role in the adjuvant setting and needs to be investigated in a multicenter setting with a long follow-up.Key words: radiotherapy - neurosurgery - magnetic resonance - pineal region - brain tumor.

Radiotherapy electron beams collimated by small tubular applicators: characterization by silicon and diamond diodes.

High-energy electron beams generated by linear accelerators, typically in the range 6 to 20 MeV, are used in small field sizes for radiotherapy of localized superficial tumors. Unshielded silicon diodes (Si-D) are commonly considered suitable detectors for relative dose measurements in small electron fields due to their high spatial resolution. Recently, a novel synthetic single crystal diamond diode (SCDD) showed suitable properties for standard electron beams and small photon beams dosimetry. The aim of the present study is twofold: to characterize 6 to 15 MeV small electron beams shaped by using commercial tubular applicators with 2, 3, 4 and 5 cm diameter and to assess the dosimetric performance under such irradiation conditions of the novel SCDD dosimeter by comparison with commercially available dosimeters, namely a Si-D and a plane­parallel ionization chamber. Percentage depth dose curves, beam profiles and output factors (OFs) were measured. A good agreement among the dosimeters was observed in all of the performed measurements. As for the tubular applicators, two main effects were evidenced: (i) OFs larger than unity were measured for a number of field sizes and energies, with values up to about 1.3, that is an output 30% greater than that obtained at the 10 × 10 cm2 reference field; (ii) for each diameter of the tubular applicator a noticeable increase of the OF values was observed with increasing beam energy, up to about 100% in the case of the smaller applicator. This OF behavior is remarkably different from what typically observed for small blocked fields having the same size and energy as those used in this study. OFs for tubular applicators depend considerably on the field size, so interpolation is unadvisable to predict the linear accelerator output for such applicators whereas reliable high-resolution detectors, as the silicon and diamond diodes used in this work allow OF measurements with uncertainties of about 1%.

Fatigue in patients undergoing radiation therapy: an observational study.

AIM: Fatigue can be defined as an unpleasant feeling of tiredness, weakness and lack of energy. It is found in about 80% of the patients receiving radiation therapy and has a significant impact on quality of life. The aim of this paper was to assess the frequency, severity and changes of fatigue before, during and after administration of a nutraceutical (mixture of whey protein with an high biological value, with an high content in native cysteine, albumin and lactoferrin in patients undergoing treatment for breast and prostate cancer. METHODS: Thirty patients (20 breast and 10 prostate ones) were enrolled in our test and they received a questionnaire about Fatigue developed by the University of Texas, MD Anderson Cancer Center, 1999. The patients who achieved a score between 4 and 6 were administered the nutraceutical (Prother) at a dose of 20 g / day for the first 10 days of radiation treatment and then 10 g/day for the following 20 days without considering the terms of the radiation oncology treatment [corrected]. Each patient was reassessed using the same Fatigue test after 10 and 30 days from the start of the administration of nutraceutical. We enrolled 30 control patients who did not receive Prother. RESULTS: The results showed the effectiveness of Prother in all patients with moderate-to-mild fatigue. CONCLUSION: The administration of Prother has therefore been effective in terms of both improving the compliance of the radiation treatment and the quality of life.

Characterization of a synthetic single crystal diamond Schottky diode for radiotherapy electron beam dosimetry.

PURPOSE: To investigate the dosimetric properties of synthetic single crystal diamond based Schottky diodes under irradiation with therapeutic electron beams from linear accelerators. METHODS: A single crystal diamond detector was fabricated and tested under 6, 8, 10, 12, and 15 MeV electron beams. The detector performances were evaluated using three types of commercial detectors as reference dosimeters: an Advanced Markus plane parallel ionization chamber, a Semiflex cylindrical ionization chamber, and a p-type silicon detector. Preirradiation, linearity with dose, dose rate dependence, output factors, lateral field profiles, and percentage depth dose profiles were investigated and discussed. RESULTS: During preirradiation the diamond detector signal shows a weak decrease within 0.7% with respect to the plateau value and a final signal stability of 0.1% (1σ) is observed after about 5 Gy. A good linear behavior of the detector response as a function of the delivered dose is observed with deviations below ±0.3% in the dose range from 0.02 to 10 Gy. In addition, the detector response is dose rate independent, with deviations below 0.3% in the investigated dose rate range from 0.17 to 5.45 Gy∕min. Percentage depth dose curves obtained from the diamond detector are in good agreement with the ones from the reference dosimeters. Lateral beam profile measurements show an overall good agreement among detectors, taking into account their respective geometrical features. The spatial resolution of solid state detectors is confirmed to be better than that of ionization chambers, being the one from the diamond detector comparable to that of the silicon diode. A good agreement within experimental uncertainties was also found in terms of output factor measurements between the diamond detector and reference dosimeters. CONCLUSIONS: The observed dosimetric properties indicate that the tested diamond detector is a suitable candidate for clinical electron beam dosimetry.

Preliminary experience of a predictive model to define rectal volume and rectal dose during the treatment of prostate cancer.

OBJECTIVES: The aim of this study was to define a method to evaluate the total dose delivered to the rectum during the whole treatment course in six patients undergoing irradiation for prostate cancer using an offline definition of organ motion with images from a cone beam CT (CBCT) scanner available on a commercial linear accelerator. METHODS: Patient set-up was verified using a volumetric three-dimensional CBCT scanner; 9-14 CBCT scans were obtained for each patient. Images were transferred to a commercial treatment planning system for offline organ motion analysis. The shape of the rectums were used to obtain a mean dose-volume histogram (), which was the average of the DVHs of the rectums as they appeared in each verification CBCT. A geometric model of an average rectum (AR) was produced using the rectal contours delineated on the CBCT scans (DVH(AR)). To check whether the first week of treatment was representative of the whole treatment course, we evaluated the DVHs related to only the first five CBCT scans ( and DVH(AR5)). Finally, the influence of a dietary protocol on the goodness of our results was considered. RESULTS: In all six patients the original rectal DVH for the planning CT scan showed higher values than all DVHs. CONCLUSION: Although the application of the model to a larger set of patients is necessary to confirm this trend, reconstruction of a representative volume of the rectum throughout the entire treatment course seems feasible.

Wolbachia surface protein (WSP) inhibits apoptosis in human neutrophils.

Polymorphonuclear cells (PMNs) are essential for the innate immune response against invading bacteria. At the same time, modulation of PMNs' apoptosis or cell death by bacteria has emerged as a mechanism of pathogenesis. Wolbachia bacteria are Gram-negative endosymbionts of filarial nematodes and arthropods, phylogenetically related to the genera Anaplasma, Ehrlichia and Neorickettsia (family Anaplasmataceae). Although several pathogens are known to interfere with apoptosis, there is only limited information on specific proteins that modulate this phenomenon. This is the first evidence for the anti-apoptotic activity of a surface protein of Wolbachia from filarial nematode parasites (the Wolbachia surface protein, WSP). The inhibition of apoptosis was demonstrated on purified human PMNs in vitro by different methods. TUNEL assay showed that the percentage of dead cells was reduced after stimulation with WSP; Annexin V-FITC binding assay confirmed that cell death was due mainly to apoptosis and not to necrosis. Reduced caspase-3 activity in stimulated cells also confirmed an inhibition of the apoptotic process.

[Surgical resection of gastrointestinal stromal tumor after treatment with imatinib: clinical case]. / Resezione chirurgica di un tumore stromale gastrointestinale dopo trattamento con imatinib: un caso clinico.

The stromal tumor is the most common mesenchymal tumor of the gastrointestinal tract. Surgical resection is the first-line therapy for operable lesions, however for inoperable imatinib is an effective therapy. In this setting a patient has been operated after a remarkable response to imatinib, used as both neoadjuvant and adjuvant. This approach led to a disease-free condition without toxicity and complications.

Blood and nutritional profiles of an individual consuming a high protein-low fat diet

This is the case of a normal weight, physically active 24-year old Puerto Rican woman consuming a highly unusual diet. Through careful selection of foods, the diet contains a high percent protein, a low percent fat, adequate fiber and zero cholesterol. Popular commercial diets high in protein all contain high fat, high cholesterol and low fiber. Blood samples were taken and dietary recalls were collected for 6 consecutive days to evaluate hematological and nutritional parameters. A blood lipid profile showed low circulating levels of cholesterol and triglycerides and a beneficial HDL/LDL ratio. However, nutritional analysis revealed insufficient ingestion of vitamin D and an unhealthy balance of servings from the food pyramid. Long-term consequences of this diet could put the subject at risk for kidney and bone diseases. Immediate discontinuation of the diet is the preferred recommendation to the subject. This case report illustrates the danger of adapting a self-prescribed eating plan without the consultation of a dietitian or other qualified health professional.

Stage I seminoma of the testis: a bi-institutional retrospective analysis of patients treated with radiation therapy only.

OBJECTIVE: To analyse relapse patterns, toxicity and second malignancy in patients with stage I pure germ cell testicular tumours, treated in 1970-1999. PATIENTS AND METHODS: In all, 487 patients received irradiation after surgery to the infra- (407, 83.5%) or infra- and supra-diaphragmatic volumes (80, 16.5%). Treatment-related toxicity was classified according to previous criteria and fertility investigated in 246 men. Second malignancies were identified by retrospective analysis of clinical records or telephone interviews in men who no longer needed a long-term follow-up. RESULTS: The 10-year overall survival was 97% (98% and 96%, respectively, for the aortic nodes only, or aortic and iliac nodes, i.e. the 'dog leg' field) and disease-free survival was 94%. Twenty-one patients relapsed (five with a true 'in-field' recurrence, nine progressed to the mediastinum, and seven had disseminated disease). Acute toxicity was mainly gastrointestinal, with 7.6% classified as grade II. In all, 73 men achieved paternity after irradiation; nine did not but had normal sperm. Second malignancies were diagnosed in 16 (3.3%) men. CONCLUSION: Para-aortic irradiation may be used safely in patients with stage I seminoma and undisturbed testicular drainage, with equivalent results to the 'dog-leg' group; these unrandomized data confirm the lower toxicity and equivalent survival rates of this treatment.

[Radiotherapy in pelvic recurrences of rectal cancer]. / La radioterapia nelle recidive pelviche da cancro del retto.

Patients with locally recurrent rectal carcinoma have an unfavourable prognosis for the high incidence of distant metastases, the infrequent feasibility of radical surgical resection, and, in these last cases, the high incidence of re-recurrences. Based on the low resectability rate of pelvic recurrences, the clear impact of tumor diameter on resectability and outcome, and the documented possibility to achieve a significant tumor downstaging and downsizing with the use of concurrent chemoradiation, it is evident that the most promising treatment several authors have considered concurrent chemoradiation followed, if feasible, by radical resection. Furthermore, based on the high local and distant failure rate after surgery, the utilization of intraoperative radiation therapy (IORT) and adjuvant chemotherapy seems justified. Some published comparisons between patients treated with and without IORT seems to suggest the possible improvement in both local control and survival in these patients. Particularly interesting issues in this field are: 1) the definition of the most effective treatment modality (both in terms of radiation dose, fractionation and techniques, and drugs to be used concurrently to radiotherapy); 2) the analysis of the prognostic impact of several factors, with the aim of designing and validating staging systems of local rectal recurrences; 3) the possibility to treat with relatively high doses also patients previously irradiated on the pelvis.

Temporal lobe (TL) damage following surgery and high-dose photon and proton irradiation in 96 patients affected by chordomas and chondrosarcomas of the base of the skull.

PURPOSE: To determine the temporal lobe (TL) damage rate in 96 patients treated with high-dose proton and photon irradiation for chordomas and chondrosarcomas of the base of the skull. METHODS AND MATERIALS: The records of 96 consecutive patients treated at Massachusetts General Hospital (MGH) and Harvard Cyclotron Laboratory (HCL) between June 1984 and 1993, for chordomas and chondrosarcomas of the base of the skull were reviewed. All the patients had undergone some degree of resection of the tumor prior to radiation therapy. Seventy-five patients were classified as "primary tumors" and 21 as recurrent or regrowing tumors after one or more surgical procedures. All the patients were randomized to receive 66.6 or 72 cobalt Gray equivalent (CGE) on a prospective dose-searching study by proton and photon irradiation (Radiation Therapy Oncology Group #85-26) with conventional fractionation (1.8 CGE/day, 5 fractions/week). All treatments were planned using the three-dimensional (3D) planning system developed at the Massachusetts General Hospital, and the dose was delivered using opposed lateral fields for the photon component and a noncoplanar isocentric technique for the proton component. Clinical symptoms of TL damage were classified into 4 grades. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans were evaluated for white matter changes. Abnormalities associated with persistent or recurrent tumor were distinguished from radiation-induced changes. TLs were delineated on the original scans of the 10 patients with damage and those of a group of 33 patients with no clinical or MRI evidence of injury. Dose distributions were calculated and dose-volume histograms were obtained for these patients. RESULTS: Of the patients, 10 developed TL damage, with bilateral injury in 2 and unilateral injury in 8. The cumulative TL damage incidence at 2 and 5 years was 7.6 and 13.2%, respectively. The MRI areas suggestive of TL damage were always separated from the tumor bed. Symptoms were severe to moderate in 8 patients. Several baseline factors, tumor- or host-related, were analyzed to evaluate their predictivity for TL damage: age, gender, tumor site, histology, type of presentation, type and number of surgical procedures, primary tumor volume, prescribed dose, normal tissue involvement, and volume of TL receiving doses ranging between 10 and 50 CGE or more. Only gender, in a univariate analysis (log rank) was a significant predictor of damage (0.0155), with male patients being at significantly higher risk of TL injury. In a stepwise Cox regression that included gender as a variable, no other baseline variable improved the prediction of damage. CONCLUSIONS: The 2- and 5-year cumulative TL damage rates were 7.6 and 13.2%, respectively. Despite the different TL damage rates related to age, tumor volume, number of surgical procedures prior to radiation therapy, and prescribed doses to the tumor, only gender was a significant predictor of damage (p = 0.0155) using a univariate (log rank) test. Chordomas and chondrosarcomas of the base of the skull may represent an interesting model to evaluate the TL damage rates because of their extradural origin, displacing the white matter instead of infiltrating it as gliomas do, because of their longer local recurrence-free survival other than gliomas and other brain tumors and because of the high doses of irradiation delivered to the target volume to obtain local control.

Magnetic resonance imaging in the measurement of clinical stage IB cervical carcinoma.

MRI can accurately define the extension of cervical carcinoma to the parametria. However, in patients with cervical carcinoma clinical stage IB, the definition of the dimensions of the tumour, prior to surgery, and may also modify the treatment procedure. Recently pre-operative neoadjuvant chemotherapy has been proposed for patients with bulky tumours. Multiple factors may influence the prognosis of clinical stage IB and survival varies greatly among these patients. In particular the maximum dimensions of the tumour seem to have a prognostic relevance. The aim of this paper is to evaluate the potential of MRI to measure tumour size, in order to discriminate between patients needing surgery alone or pre-operative therapy followed by surgery. In 20 patients with clinical stage IB cervical carcinoma we performed MRI to measure the radius of the cervix, the radius of the tumour and their ratios. The measurements obtained have been compared with the corresponding data from histopathology of the operative specimens. The close correspondence between these linear measurements allows us to propose MRI as a reliable method to define tumour size in clinical stage IB patients before surgery.

Clinical stage IIb carcinoma of the uterine cervix: results in 122 patients.

122 patients affected by clinical stage IIb cervical carcinoma were referred to the Radiation Therapy Department and Obstetrics and Gynaecology Department of the University of Florence between 1977 and 1986 for either radiation therapy only (42 patients) or preoperative treatment followed by surgical resection (80 patients). Among the 42 patients receiving radiation therapy only 23 were treated with external beam therapy only (total dose ranging between 50 Gy and 70 Gy at the mid-plane of the pelvis) while 19 received an additional intracavitary boost (total dose ranging between 68 Gy and 98 Gy at Manchester point A). Higher doses of irradiation to point A were correlated with significantly improved survival (65% vs. 18.5%, p = 0.001) and lower incidence of pelvic failure (33% vs 78%). Following preoperative radiation therapy 80 patients underwent radical surgery. Reassessment of the pathologic specimens was possible in all the cases. Disease free survival was not influenced by involvement of parametria, type of surgery or dose to Manchester point A, but rather to nodal status and thickness of the residual tumour in the cervix.

Reliability of volume or age-adjusted prostate specific antigen to improve diagnostic accuracy.

Prostate Specific Antigen (PSA), PSA density, PSA excess, and PSA age-specific range have been compared in 331 subjects (35 cancers, 296 benign) with equivocal findings at screening by PSA or palpation+transrectal ultrasonography. The specificity of PSA using a cut-off of 4 ng/ml was only 0.49. A cutoff of 10 ng/ml improved the specificity to 0.88 but the sensitivity decreased from 0.97 to 0.63. The sensitivity and specificity for PSA density (cutoff 0.15), PSA excess (cutoff -5), and age-specific range were 0.86 and 0.80, 0.80 and 0.82, and 0.91 and 0.67, respectively. Avoided benign biopsies vs missed cancers on the basis of PSA density, PSA excess and PSA age-specific range would have been 19 and 5, 26 and 7, and 16 and 3, respectively. Methods adjusting for prostate volume allow a better interpretation of PSA values and may reduce the benign biopsy rate, but the consequent cost of delayed cancer diagnoses when the choice of biopsy is based only on these methods seems unacceptable.

Comparing two modalities of screening for prostate cancer: digital rectal examination + transrectal ultrasonography vs. prostate-specific antigen.

AIMS AND BACKGROUND: To evaluate the performance and feasibility of screening for prostate cancer by comparing screening modalities. METHODS: Prospective study of two comparable cohorts of healthy resident males aged 60 to 75 years. Screening attenders in the two invited cohorts were screened either by digital rectal examination (DRE) and transrectal ultrasonography (TRUS), or by serum prostate-specific antigen determination (PSA: cutoff 4 ng/ml). Attendance and biopsy rates, predictive values, prevalence of screen-detected cancers, as well as screening costs were determined, and the efficiency of the two screening modalities was compared. RESULTS: 1425 subjects were screened by DRE+TRUS. Attendance rate was 33.7%, the biopsy rate was 2.7%, and the prevalence of detected cancers was 1.82%. A total of 1315 subjects was screened by PSA. Attendance rate was 66.9%, the biopsy rate was 2.8%, and the prevalence of detected cancers was 1.67%. Screen-detected cancer stage was more favorable than observed in clinical practice, and early detection was evident, with the prevalence/incidence ratio higher than 10:1 in both programs. The cost per subject screened was about 34,000 Lire for DRE+TRSU and about 30,000 Lire for PSA program. CONCLUSIONS: The study confirms that early detection of prostate cancer is possible and that screening is practically feasible. Both screening modalities achieved comparable results as regards early detection, but screening by PSA had a higher compliance and lower costs. PSA seems the ideal test to be used in prospective controlled studies aimed at demonstrating screening efficacy.

Technical note: multimedia clinical records: results of a pilot project at the Radiation Therapy Department of Florence.

A system based on Macintosh, Hypercard and a local network was developed at the University and Hospital Department of Radiation Therapy, Florence, Italy, to manage the clinical records as a complex data structure (data, texts, drawings and image storage and retrieval). After 4 years, the system produces over 2000 new charts a year and manages more than 15,000 clinical records. Electronic records are produced, printed and updated in their traditional form to be put on file in our archive. On-line consultation of the clinical records is possible from every workstation of the structure even as it is producing, updating, or printing a chart. Physicians and clinical clerks, with different access privileges, currently use the system for all these purposes. The clinical records are typed by secretaries who receive dictation on microcassettes. No extra staff were necessary to set up and manage the system and training was simple. The new system changed neither the organization and structure of the traditional records, nor the flux of information; new tools (computers, printers and a network) were introduced to manage the information and the charts. The author describes the aims of the original project and the results.

[Comparison between 2 techniques of screening for prostatic carcinoma. Rectal exploration and transrectal ultrasonography vs. prostate specific antigen]. / Confronto tra due modalità di screening per il carcinoma prostatico. Esplorazione rettale ed ecografia transrettale vs. antigene prostatico specifico.

We report the results of two pilot studies for the early detection of prostatic carcinoma in resident men aged 60-75 years, using combined digital rectal examination (DRE) and transrectal ultrasonography (TRUS) versus prostate-specific antigen (PSA; cutoff: 4 ng/ml) as screening tests. Both screening protocols exhibited high cancer detection rates (DRE + TRUS = 1.82%, PSA = 1.67%), with a high prevalence/incidence ratio (observed/expected ratio: DRE-TRUS = 13.8:1, PSA = 11.3:1) and a diagnostic anticipation of about 6-7 years. Stage (DRE + TRUS: A = 0%, B = 69%, C-D = 31%; PSA:A = 14%, B = 77%, C-D = 9%) and grading distribution (no case with Gleason score < 5) suggests that most screen-detected cancers were clinically assessable but the extent of overdiagnosis of latent carcinomas cannot be estimated. Both screening protocols proved to be cost-effective (biopsy rate: DRE + TRUS = 2.7%, PSA = 2.8%; cost per screened subject: DRE + TRUS = L. 33,750, PSA = L. 30,400; cost per cancer detected: DRE + TRUS = L. 1,854,000, PSA = L. 1,817,500) but screening by PSA was much better accepted (attendance rate: DRE + TRUS = 33.7%, PSA = 66.9%), which makes it the screening test of choice for controlled studies on screening efficacy. This study allows no definitive conclusions to be drawn on screening efficacy but confirms only that screening is feasible at a reasonable cost and yields high diagnostic anticipation. Whether this benefits the screened population is currently debated and needs to be confirmed by controlled studies. Screening may have upsetting negative outcomes such as overdiagnosis, overtreatment, increased treatment-related mortality rates and worsened quality of life, and there is no evidence supporting the recommendation of screening as a routine practice.