Short fractionation radiotherapy for early prostate cancer in the time of COVID-19: long-term excellent outcomes from a multicenter Italian trial suggest a larger adoption in clinical practice.

INTRODUCTION: To evaluate stereotactic body radiotherapy (SBRT) in low-risk Prostate Cancer patients as preferred treatment option in emergency health conditions. MATERIALS AND METHODS: From April 2013 to September 2015, 28 patients with low-risk prostate cancer were prospectively enrolled. The SBRT prescribed dose was 36.25 Gy in 5 fractions, twice a week. Primary endpoints were acute and late toxicity. Secondary endpoints were biochemical recurrence free survival (bRFS) and overall survival. RESULTS: Median follow-up was 65.5 months (range 52-81). No acute G3 or G4 toxicity was recorded. Acute G1 or G2 genitourinary (GU) toxicity occurred in 43% and acute G1-G2 gastrointestinal (GI) toxicity in 14%. Late G1 and G3 GU toxicity in 18% and 3.5%, respectively. The G3 toxicity was not directly attributable to radiotherapy. Late G1 GI toxicity occurred in 18%. 5yy bRFS was 96.5% (95% CI 82.3-99.4%). CONCLUSIONS: Stereotactic body radiotherapy for early prostate cancer reported safe toxicity profile and a good clinical outcome at the median follow-up of 5 years. It may be an useful option if radiotherapy is required in emergency medical conditions.

Diverse Imaging Methods May Influence Long-Term Oncologic Outcomes in Oligorecurrent Prostate Cancer Patients Treated with Metastasis-Directed Therapy (the PRECISE-MDT Study).

Metastasis-directed therapy (MDT) has been tested in clinical trials as a treatment option for oligorecurrent prostate cancer (PCa). However, there is an ongoing debate regarding the impact of using different imaging techniques interchangeably for defining lesions and guiding MDT within clinical trials. Methods: We retrospectively identified oligorecurrent PCa patients who had 5 or fewer nodal, bone, or visceral metastases detected by choline or prostate-specific membrane antigen (PSMA) PET/CT and who underwent MDT stereotactic body radiotherapy with or without systemic therapy in 8 tertiary-level cancer centers. Imaging-guided MDT was assessed as progression-free survival (PFS), time to systemic treatment change due to polymetastatic conversion (PFS2), and overall survival predictor. Propensity score matching was performed to account for clinical differences between groups. Results: Of 402 patients, 232 (57.7%) and 170 (42.3%) underwent MDT guided by [18F]fluorocholine and PSMA PET/CT, respectively. After propensity score matching, patients treated with PSMA PET/CT-guided MDT demonstrated longer PFS (hazard ratio [HR], 0.49 [95% CI, 0.36-0.67]; P < 0.0001), PFS2 (HR, 0.42 [95% CI, 0.28-0.63]; P < 0.0001), and overall survival (HR, 0.39 [95% CI, 0.15-0.99]; P < 0.05) than those treated with choline PET/CT-guided MDT. Additionally, we matched patients who underwent [68Ga]Ga-PSMA-11 versus [18F]F-PSMA-1007 PET/CT, observing longer PFS and PFS2 in the former subgroup (PFS: HR, 0.51 [95% CI, 0.26-1.00]; P < 0.05; PFS2: HR, 0.24 [95% CI, 0.09-0.60]; P < 0.05). Conclusion: Diverse imaging methods may influence outcomes in oligorecurrent PCa patients undergoing MDT. However, prospective, head-to-head studies, ideally incorporating a randomized design, are necessary to provide definitive evidence and facilitate the practical application of these findings.

The Role of mpMRI in the Assessment of Prostate Cancer Recurrence Using the PI-RR System: Diagnostic Accuracy and Interobserver Agreement in Readers with Different Expertise.

BACKGROUND: treated prostate cancer (PCa) patients develop biochemical recurrence (BCR) in 27-53% of cases; the role of MRI in this setting is still controversial. In 2021 a panel of experts proposed a "Prostate Imaging-Recurrence Reporting" (PI-RR) score, aiming to standardize the reporting. The aim of our study is to evaluate the reproducibility of the PI-RR scoring system among readers with different expertise. METHODS: in this monocentric, retrospective observational study, the images of patients who underwent MRI with BCR from January 2017 to January 2022 were analyzed by two radiologists and a radiology resident. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were obtained. Interobserver agreement was calculated. The percentage of the PI-RR score of 3 was estimated to find out the proportion of uncertain exams reported among the readers. RESULTS: a total of seventy-six patients were included in our study: eight previously treated with RT and sixty-eight who underwent surgery. The accuracy range was 75-80%, the sensitivity 68.4-71.1%, the specificity 81.6-89.5%, PPV 78.8-87.1%, and NPV 72.1-75.6%. The inter-reader agreement using a binary evaluation (PI-RR ≥ 3 as positive mpMRI) demonstrated a correlation coefficient (k) of 0.74 (95% CI: 0.62-0.87). The percentage for the PI-RR score of 3 was 6.6% for reader one, 14.5% for reader two, and 2.6% for reader three. CONCLUSION: this study confirmed the good accuracy of mpMRI in the detection of local recurrence of PCa and the good reproducibility of PI-RR score among all readers, confirming it to be a promising tool for the standardization of the assessment of patients with BCR.

The prognostic value of FIGO staging defined by combining MRI and [18F]FDG PET/CT in patients with locally advanced cervical cancer.

The last version of the FIGO classification recommended imaging tools to complete the clinical assessment of patients with cervical cancer. However, the preferable imaging approach is still unclear. We aimed to explore the prognostic power of Magnetic Resonance Imaging (MRI), contrast-enhanced Computed Tomography (ceCT), and [18F]-Fluorodeoxyglucose Positron Emission Tomography ([18F]FDG-PET)/CT in patients staged for locally advanced cervical cancer (LACC, FIGO stages IB3-IVA). Thirty-six LACC patients (mean age 55.47 ± 14.01, range 31-82) were retrospectively enrolled. All of them underwent MRI, ceCT and [18F]FDG-PET/CT before receiving concurrent chemoradiotherapy. A median dose of 45 Gy (range 42-50.4; 25-28 fractions, 5 fractions per week, 1 per day) was delivered through the external-beam radiation therapy (EBRT) on the pelvic area, while a median dose of 57.5 Gy (range 16-61.1; 25-28 fractions, 5 fractions per week, 1 per day) was administered on metastatic nodes. The median doses for brachytherapy treatment were 28 Gy (range 28-30; 4-5 fractions, 1 every other day). Six cycles of cisplatin or carboplatin were administered weekly. The study endpoints were recurrence-free survival (RFS) and overall survival (OS). Metastatic pelvic lymph nodes at MRI independently predicted RFS (HR 13.271, 95% CI 1.730-101.805; P = 0.027), while metastatic paraaortic lymph nodes at [18F]FDG-PET/CT independently predicted both RFS (HR 11.734, 95% CI 3.200-43.026; P = .005) and OS (HR 13.799, 95% CI 3.378-56.361; P < 0.001). MRI and [18F]FDG-PET/CT findings were incorporated with clinical evidences into the FIGO classification. With respect to the combination of clinical, MRI and ceCT data, the use of next-generation imaging (NGI) determined a stage migration in 10/36 (27.7%) of patients. Different NGI-based FIGO classes showed remarkably different median RFS (stage IIB: not reached; stage IIIC1: 44 months; stage IIIC2: 3 months; P < 0.001) and OS (stage IIB: not reached; stage IIIC1: not reached; stage IIIC2: 14 months; P < 0.001). A FIGO classification based on the combination of MRI and [18F]FDG-PET/CT might predict RFS and OS of LACC patients treated with concurrent chemoradiotherapy.

Oligometastatic Prostate Cancer Treated with Metastasis-Directed Therapy Guided by Positron Emission Tomography: Does the Tracer Matter?

The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa patients treated with [68Ga]Ga-PSMA-11 PET-guided metastasis-directed therapy (MDT). The present study aimed to assess the impact of these two imaging techniques on Progression-Free Survival (PFS) in a real-world sample of oligometastatic PCa patients submitted to PET-guided MDT. Thirty-seven oligometastatic PCa patients treated with PET-guided MDT were retrospectively enrolled. MDT was guided by [18F]F-Fluorocholine PET/CT in eleven patients and by [68Ga]Ga-PSMA-11 PET/CT in twenty-six. Progression was defined as biochemical recurrence (BR), radiological progression at subsequent PET/CT imaging, clinical progression, androgen deprivation therapy initiation, or death. Clinical and imaging parameters were assessed as predictors of PFS. [18F]F-Fluorocholine PET-guided MDT was associated with significantly lower PFS compared to the [68Ga]Ga-PSMA-11 group (median PFS, mPFS 15.47 months, 95% CI: 4.13−38.00 vs. 40.93 months, 95% CI: 40.93−40.93, respectively; p < 0.05). Coherently, the radiotracer used for PET-guided MDT resulted in predictive PFS at the univariate analysis, as well as the castration-resistant status at the time of MDT and the PSA nadir after MDT. However, in the multivariate analysis, castration resistance and PSA nadir after MDT remained the sole independent predictors of PFS. In conclusion, in the present proof-of-concept study, [68Ga]Ga-PSMA-11 provided higher PFS rates than [18F]F-Fluorocholine imaging in oligometastatic PCa patients receiving PET-guided MDT. Although preliminary, this finding suggests that enlarging the "tip of the iceberg", by detecting a major proportion of the submerged disease thanks to next-generation imaging may favourably impact the oncological outcome of oligometastatic PCa treated with MDT.

A phase II trial of low-dose gemcitabine and radiation alternated to cisplatin and 5-fluorouracil: an active and manageable regimen for stage IV squamous cell carcinoma of the head and neck.

BACKGROUND: The addition of gemcitabine may be a reasonable way to enhance the activity of the alternating cisplatin/5-fluorouracil and radiation regimen considered the referring approach for patients with advanced squamous cell carcinoma (SCC) of the head and neck at the National Institute for Cancer Research of Genoa. METHODS: Three courses of cisplatin, 20mg/m(2)/day and 5-fluorouracil, 200mg/m(2)/day, days 1-5 (weeks 1, 4, and 7) alternated to 3 courses of radiotherapy at standard fractionation (weeks 2-3, 5-6, 8-9) up to 60Gy, and gemcitabine, 50mg/m(2) on monday of each week of radiation, were administered to 47 patients with stage IV (42 patients) or relapsed after surgery (5 patients), SCC of the oral cavity, pharynx or larynx. RESULTS: Eighty-five percent of the patients completed the planned treatment. Main grade 3-4 acute toxicities were: mucositis (40%), neutropenia (26%) and thrombocytopenia (30%). Twenty-seven patients reached a complete response (57%). Seven partial responders were rendered disease-free by surgery (final complete response rate: 72%). At a median follow-up of 37 months, 3-year overall survival, progression-free survival and loco-regional control are 50%, 43% and 54%, respectively. CONCLUSIONS: The addition of gemcitabine at low dose to our referring alternating regimen is feasible and very active. It may improve the long-term outcomes despite an acceptable increase of acute mucoseal toxicity.

Induction chemotherapy followed by alternating chemo-radiotherapy in non-endemic undifferentiated carcinoma of the nasopharynx: optimal compliance and promising 4-year results.

Concomitant chemo-radiotherapy is the standard treatment for advanced nasopharyngeal carcinoma (NPC). Induction chemotherapy may improve the results further by enhancing both loco-regional and distant control. Fifty patients with untreated, stage IV (UICC 1992) undifferentiated NPC were initially treated with three courses of epidoxorubicin, 90 mg/m(2), day 1 and cisplatin, 40 mg/m(2), days 1 and 2, every three weeks and then underwent three courses of cisplatin, 20 mg/m(2)/day, days 1-4 and fluorouracil, 200mg/m(2)/day, days 1-4 (weeks 1, 4, 7), alternated to three splits of radiation (week 2-3, 5-6, 8-9-10) up to 70 Gy. All patients but one received 3 cycles of induction chemotherapy. Toxicities from induction chemotherapy were grade III or IV mucositis (2%), grade III or IV nausea/vomiting (22%), grade III or IV hematological toxicity (6%). At the end of induction phase 12% of CRs, 84% of PRs were recorded. Toxicities from alternating chemo-radiotherapy were grade III or IV mucositis (30%), grade III or IV nausea/vomiting (8%), grade III or IV hematological toxicity (24%). Overall, 86% of CRs and 14% of PRs were observed. Four-year progression free survival and overall survival rates are 71% and 81%, respectively. In a small number of patients studied, no correlation between the level of EGFR overexpression and outcomes was detected. In locally advanced UNPC our combined program including induction chemotherapy followed by alternating chemo-radiotherapy is active and gives promising long-term outcomes with acceptable toxicity and optimal patients' compliance. This program merits to be tested in a phase III trial.

Moderate hypofractionated radiotherapy after prostatectomy for cancer patients: toxicity and clinical outcome.

Background: After radical prostatectomy (RP) radiotherapy (RT) plays a role, both as adjuvant or salvage treatment. If negative features are present such as extracapsular extension, seminal vesicle invasion, lymph invasion, and positive surgical margins, RT after RP reduces the risk of recurrence, although it is associated with an increased risk of acute and late toxicities. An intensified RT delivered in a shortened time could improve clinical outcome and be safely combined with hormonal therapy (HT). The aim of this study was to determine the acute and late toxicities associated with hypofractionated RT and to assess the impact of the addition of HT to RT in high-risk prostate cancer (PC) patients on overall response and toxicity. Materials and methods: Sixty-four PC patients undergoing RP were included in this retrospective study. All patients were recommended to receive adjuvant or salvage RT. Prescription doses were 62.5 Gy in 25 fractions to prostate bed, 56.25 Gy in 25 fractions to seminal vesicles bed, and 50 Gy in 25 fractions to pelvis if indicated. HT was administered to patients with additional adverse pathologic features including Gleason score >7, prostate-specific antigen >20 ng/mL before surgery, or prostate-specific antigen with rapid doubling time after relapse or nodal involvement. After completion of RT, patients were observed after 4 weeks, and then followed-up every 3-6 months. Acute and late toxicities were assessed using Common Terminology Criteria for Adverse Events v4 and Radiation Therapy Oncology Group scale, respectively. Results: For acute toxicity, only grade 1 gastrointestinal and genitourinary toxicities were detected in 17% and 11% of patients, respectively. As regards late toxicity, only 5% of the patients developed grade 1 gastrointestinal adverse event; grade 1, grade 2, and grade 3 genitourinary toxicity was recorded in 5%, 3.3%, and 3.3% of patients, respectively. Two and 5 years overall survival were 98% and 96%, respectively. The curves stratified for treatment show a slight difference between patients receiving RT or RT+HT, but the differences did not reach statistical significance (p=0.133). Conclusion: In patients with PC undergoing RP, hypofractionated RT may contribute to achieve a high overall survival with an acceptable toxicity profile. Combination of RT and HT is also well tolerated and efficacious.

Complete response in a patient with gynecological hidradenocarcinoma treated with exclusive external beam radiotherapy and brachytherapy: a case report.

Hidradenocarcinoma (HC) is a very rare disease. This case report illustrates a successful treatment of a 60-year-old woman with vulvo-vaginal localization of hidradenocarcinoma treated with external beam radiotherapy delivered by helical tomotherapy with a simultaneous integrated boost (SIB), followed by brachytherapy. External beam radiotherapy dose prescription was 50.4 Gy in 28 fractions, five fractions per week to whole pelvis (planning target volume 1 - PTV1), 60.2 Gy in 28 fractions to SIB1 (fundus of uterus and right inguinal node), and 58.8 Gy in 28 fractions to SIB2 (lower/middle third of vagina, paraurethral region and right inguinal lymph nodes). Brachytherapy dose prescription was 28 Gy in 4 fractions for cervix, fundus of uterus and upper third of vagina (HR-CTV1), and 22 Gy in 4 fractions to middle third of vagina and paraurethral region (HR-CTV2). D90 for whole treatment was 91.9 Gy and 86.0 Gy for HR-CTV1 and HR-CTV2, respectively. Patient remained 12-months disease-free without treatment related side effects.

Kidney-sparing radiotherapy by multiple-field three-dimensional technique in the postoperative management of patients with gastric cancer: comparison with standard two-field conformal technique.

AIMS AND BACKGROUND: The opposed two-field technique is the standard approach for delivering adjuvant radiotherapy to patients with resected gastric cancer. Since a considerable radiation dose may reach both kidneys with this beam arrangement, with a potential risk of late effects, we investigated whether the CT-based multiple-field (M-F) approach was superior in terms of sparing critical organs at risk. METHODS: From March 2001 to March 2004, 19 patients with radically resected gastric cancer entered the study. They were treated with adjuvant chemoradiotherapy according to the INT 0116 protocol. For each patient dose-volume histograms were calculated and the volume values of both kidneys and liver receiving 25 Gy (V25), 30 Gy (V30) and 40 Gy (V40) individually estimated with the M-F and two-field techniques were compared in detail. RESULTS: Right kidney median V25, V30 and V40 values for the two-field and M-F techniques were 1.50%, 0%, 0% and 0%, 0% and 0%, respectively (P < 0.005, P < 0.01, P < 0.05). Left kidney median V25, V30 and V40 values for the M-F and two-field technique were 16%, 9.80%, 0.90% and 33.20%, 30.20%, 21.40% (P < 0.001, P < 0.0005, P < 0.0005). Liver median V25, V30 and V40 values for the M-F and two-field techniques were 51.30%, 22.30%, 8.90% and 13.30%, 11.60%, 8.10%, respectively (P < 0.0001, P < 0.0005 and P = 0.18). CONCLUSIONS: Our comparison revealed that with the multiple-field technique the right kidney may be largely spared from irradiation; with respect to the two-field technique, the left kidney may receive a significantly reduced dose; however, the liver receives an increased dose that warrants careful long-term monitoring of hepatic function.

Excellent survival regardless of disease stage in patients with advanced nasopharyngeal cancer.

BACKGROUND: We present our experience in assessing the feasibility and efficacy outcomes of intensified intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) delivered to patients with nasopharyngeal carcinoma (NPC). METHODS: Between March 2009 and December 2014, 35 patients affected by advanced NPC with a median age of 53 years (range 11-77) were treated with definitive radiotherapy. Radiotherapy was delivered by helical tomotherapy with the SIB technique. The prescribed doses were 66 Gy to macroscopic disease, 60 Gy to high-risk subclinical disease, and 54 Gy to low-risk disease in 30 fractions. The daily SIB dose was 2.2 Gy to macroscopic disease. RESULTS: At the end of treatment 33 (94%) patients had obtained complete clearance of disease and 2 patients had died (1 of persistent disease after 3 months and 1 of cancer-unrelated causes after 4 months). At a median follow-up of 40 months (range 5-69), locoregional control rates at 2 and 4 years were 92.9% and 88.2%, respectively, and the overall survival after 4 years was 93.9%. The most significant acute toxicities were grade 2 and 3 mucositis (43%). No grade 3 and 4 late toxicities were observed; grade 2 xerostomia after 6 months from the end of treatment was reported in 11 patients; xerostomia toxicity decreased to grade 1 in 6/11 patients within 12 months. CONCLUSIONS: These results show that intensified IMRT with SIB is an excellent strategy offering high local control rates for NPC patients with mild acute and late toxicity.

Rectal and bladder motion during conformal radiotherapy after radical prostatectomy.

BACKGROUND AND PURPOSE: To investigate the extent and the impact of rectum and bladder motion during adjuvant conformal radiotherapy (3DCRT) after radical prostatectomy (RP). MATERIALS AND METHODS: Nine patients previously operated with RP and treated with early adjuvant 3DCRT were considered for this investigation. Weekly CT scans were collected during treatment (CT1-CTn, n=4-6) and were 3D matched using bony anatomy with the planning CT (CT0). A single observer drew the contours of rectum and bladder on all CTs. The CTV (prostate+/-seminal vesicles surgical bed) was contoured on CT0 by a single observer and a 4-field 3DCRT technique was planned: dose statistics/dose-volume histograms (DVH) of the rectum and bladder were calculated for each contour referred to CT0, CT1...CTn. Average DVHs during the treatment were then calculated and compared with the planned DVH. Cranial, caudal, anterior and posterior shifts of rectum and bladder were also assessed by lateral BEV projections. NTCP values for the rectum were also calculated using the Lyman-Kutcher model. RESULTS: Random variations of volume and DVHs due to variable filling content were found for the bladder; a trend of the bladder to be more empty during therapy with respect to CT0 was also found (median values: 45 cm3 vs. 79 cm3, P=0.02). Regarding the rectum, 6/9 patients showed an average DVH 'worse' than the planned one (up to 10-20%). BEV and volume analyses showed that the rectal volume decreased in 3/9 patients after the first week. In 6/9 patients a systematic anterior shift of the cranial half of the rectum was detected and found to be correlated with a corresponding shift of the posterior border of CTV contoured by five different observers. The average rectal NTCP during therapy was systematically higher than the NTCP referred to CT0 (average increase 1.2%; range 0.0-3.7%, for a 70 Gy ICRU dose, P=0.01). CONCLUSIONS: The impact of systematic uncertainty due to rectal wall motion seems to be relatively high for patients treated with adjuvant 3DCRT after RP. The detected trend of the rectum in migrating anteriorly during therapy is consistent with post-surgery settlement effects and/or some modification of rectum mobility due to irradiation. Rectal motion (and consequent shifts of CTV) was large at the half cranial portion of the rectum while it was very small below the flexure.

Neoadjuvant androgen deprivation and prostate gland shrinkage during conformal radiotherapy.

PURPOSE: The shrinking effect of 3-month neoadjuvant androgen deprivation (NAD) on preradiotherapy prostate gland volume is well documented. However, recently, it has been shown that the cancerous prostate gland keeps shrinking up to 12 months after NAD start. Thus, if such a reduction is not taken into account, a larger than planned portion of the surrounding normal tissues might shift in the high-dose region during conformal radiotherapy (3DCRT) course. The present study was undertaken to quantify this issue. MATERIALS AND METHODS: Prostate gland volume reduction between planning CT (plCT) and the last week of 3DCRT (tmtCT) was prospectively assessed in 33 consecutive patients with localized prostate carcinoma. The median time interval between plCT and tmtCT was 2.5 months (2.1-2.7 months). A single observer was asked to draw on each slice prostate gland volume as appropriate. The observer was 'blind' to the timing of CT (plCT vs. tmtCT). In order to estimate intra-observer variability, prostate gland delineation was repeated twice for each data set. Mean prostate gland change, plCT and tmtCT cumulative dose volume histogram (DVH) calculations for the rectum were analyzed for each patient. Results were correlated to AD status and its duration before plCT. Means were compared by non-parametric rank tests. RESULTS: Based on an internal protocol, 14 patients (42%) did not receive AD, while 19 patients (58%) had undergone neoadjuvant and concomitant AD. The median duration of AD before plCT ranged from 0.2 to 6 months (median: 2.9 months). Although individual data were highly variable, compared to plCT volume, mean prostate gland volume change at the end of 3DCRT was similar for patients receiving (-7.3%) or not (-7%) androgen deprivation (P=0.77). However, within the group of patients treated with hormones, patients starting AD within 3 months from plCT had a significantly larger reduction in prostate volume (-14.2%) than patients with longer NAD duration (-1.1%, P=0.03). At tmtCT, on average, patients undergoing 3DCRT within 3 months from AD start showed an increase of the amount of rectum receiving 40-75 Gy compared to plCT values. At 40 Gy (V40) the mean difference between tmtCT and plCT was +7.5%. In the other two groups, average variations of V40-70 were within +/-2% of plCT values. However, these differences are not significant. CONCLUSION: For patients who undergo plCT and 3DCRT shortly after AD start, prostate gland shrinkage may be substantial. In some of these patients, this might lead to an unexpected increase of the percentage of rectal wall exposed to intermediate doses.

Audit of effectiveness of routine follow-up clinics after radiotherapy for cancer: a report of the REACT working group of ESTRO.

BACKGROUND AND PURPOSE: The European Society for Therapeutic Radiology and Oncology was funded by the EU for a project on recording providing education, and ameliorating the consequences of treatment (REACT). An European audit was carried out as part of which to assess the usefulness of current follow-up practices. PATIENTS AND METHODS: Over a 4-month period in 15 cancer centres in 10 countries, patients attending for routine follow-up completed a questionnaire covering their expectations of and satisfaction with the visit. This was matched with a questionnaire completed by the physician about the content and usefulness of the consultation. The feasibility of a short toxicity scale developed by Dische and Saunders was also investigated. RESULTS: In total, 2303 matched questionnaires were analysed. Forty percent of the patients had symptoms or medical problems related to their disease. In 18% there was a positive finding on clinical examination. In 28% investigations were undertaken part of departmental routine practice. Ten percent of the investigations showed an abnormal result. Ninety nine percent of physicians and 85% of the patients expressed satisfaction. Using the short toxicity scale rates of recording toxicity could be increased from 28 to 93%. CONCLUSIONS: There is wide variation in follow-up practices among European centres. There was a low incidence of positive findings clinically or with routine investigations. A simple scale for recording morbidity has proved easy to use by departments, which have not routinely used one of the standard measures. Further work will attempt to produce an European guideline for effective routine follow-up after radiotherapy.

Radiotherapy after prostatectomy.

AIMS AND BACKGROUND: The role of radiotherapy after prostatectomy is controversial. This paper tries to give some guidelines for everyday practice through an analysis of literature data. METHODS: The potential role of radiotherapy in the adjuvant and salvage setting is discussed. We also report and interpret available literature data for both settings. RESULTS: As regards an increase in or detectable prostate-specific antigen (PSA) after radical prostatectomy, about 40-50% of patients are rendered bNED with local salvage radiotherapy, but only 10-50% are long-term (5 years) biochemically controlled. A timely salvage treatment is crucial to optimize control probability. As regards adjuvant radiotherapy for undetectable postoperative PSA in patients at high risk of failure as judged on pathology, results are more encouraging. Recent data report bNED rates > 70% at 5 years. CONCLUSIONS: Although results are far from satisfactory, salvage radiotherapy should be considered for every patient with an increased or detectable PSA after surgery. Adjuvant radiotherapy seems preferable to salvage radiotherapy for patients at high (> 30%) risk of failure.

Radiotherapy and oral capecitabine in the preoperative treatment of patients with rectal cancer: rationale, preliminary results and perspectives.

Preoperative radiotherapy alone or combined with chemotherapy increases the chances of tumor down-staging and down-sizing and facilitates sphincter-sparing surgical procedures, thereby improving survival and quality of life. Though several innovative agents are being investigated in combination with radiotherapy, 5-fluorouracil in continuous infusion remains the common schedule used in the preoperative chemoradiation setting. However, the protracted venous infusion of 5-fluorouracil requires specialized pumps and long-term venous access, which makes patients susceptible to infections or thrombosis. To overcome the 5-fluorouracil infusion-related problems, oral 5-fluorouracil precursors and inhibitors of 5-fluorouracil degradation have been developed and explored. These include oral fluoropyrimidines such as tegafur (ftorafur), uracil plus tegafur (UFT), S-1, eniluracil and the oral carbamate capecitabine. Phase I trials have demonstrated the feasibility of the capecitabine-radiotherapy combination with respect to the bolus or infusion 5-fluorouracil-radiation approach and have defined the optimal dose of capecitabine during radiotherapy (825 mg/m2/day through a bid administration). Severe hand-foot syndrome occurred in 7-15% of patients, representing the most commonly observed toxicity. It is noteworthy that severe diarrhea with capecitabine during radiotherapy was not common. Leukopenia frequently occurred but was mild and reversible. Phase II trials, although limited in number, have evidenced a high probability of pathological complete response (up to 31%) with capecitabine and radiation, with an increased probability of sphincter-sparing surgical procedures. Although it is too early to assess whether oral capecitabine will be able to replace iv 5-fluorouracil in combination with preoperative radiotherapy, the NSABP will address this question in a large randomized trial. Finally, phase I-II trials evaluating escalating doses of capecitabine associated with oxaliplatin or irinotecan with radiotherapy are being carried out to assess the maximum-dose tolerance and efficacy in the preoperative setting. It is likely that these new chemoradiation associations might increase rectal cancer clearance, hopefully without increasing toxicity.

Measures of late effects in conservative treatment of breast cancer with standard or hypofractionated radiotherapy.

AIMS AND BACKGROUND: To confirm the equivalence in terms of late effects between two fractionation schedules of radiotherapy in conservative treatment of breast cancer. METHODS: Fifty-eight patients treated at our institution from 1999 to 2002, with a median follow-up of 15 months (range, 7-46 months), were evaluated retrospectively. Twenty-nine patients (group A) were treated with standard fractionation: 5000 cGy/25fx/5 weeks, and 29 patients (group B) were treated with a hypofractionated schedule: 4500 cGy/15fx/5 weeks, three fractions per week. Late effects were evaluated using the LENT-SOMA scoring scale. The cosmetic results were assessed on a five-point scale. Skin elasticity was measured using a dedicated device (Cutometer SEM 575). RESULTS: There were no differences in breast volume, age at diagnosis and follow-up between groups. The LENT-SOMA toxicity observed in groups A and B, respectively, was as follows: grade 2-3 pain in five patients in each group; grade 2 breast edema in two and three patients; grade 2-3 and grade 2 fibrosis in six and eight patients; grade 2 and grade 2-3 telangiectasia in two and three patients; grade > or = 2 and 2 arm edema in two and one patients; no ulceration or atrophy were observed. Two patients in group A and one patient in group B needed treatment for breast and arm edema and arm edema, respectively. Very good, good-acceptable, and poor cosmetic results were observed in seven and two, fifteen and nineteen, and six and eight patients, respectively. Median skin elasticity loss due to treatment was -4.19% in group A and -6.29% in group B. These results are not statistically different. CONCLUSIONS: LENT-SOMA toxicities were minimal and no differences were observed between groups. Few patients in the hypofractionated group had very good cosmetic results, but it is debatable if radiotherapy was the only cause. Skin elasticity was not different between groups. Our results seem to suggest that it is possible to treat patients with both schedules, with similar late toxicity.

Late local treatment morbidity after accelerated radiotherapy or alternating chemoradiotherapy for advanced head and neck carcinoma.

BACKGROUND: To report local long-term morbidity after concomitant boost radiotherapy (AFRT) or alternating chemoradiotherapy (CTRT), we analyzed the toxicity data recorded in 168 patients with advanced head and neck squamous cell carcinoma treated at our institution within phase II-III studies. PATIENTS AND METHODS: All patients enrolled in three consecutive phase II-III studies and followed for a minimum of three months after the end of treatment were included in the present analysis. Local late reactions were scored prospectively. The actuarial incidence of grade 2 or more (2-4) late local toxicity according to RTOG/EORTC was taken as endpoint. The median follow-up is 32.0 months (range, 3.3-138.1 months). For living patients the minimum and median follow-up are 12.1 and 69.3 months, respectively. RESULTS: The five-year actuarial incidence of grade 2+ and grade 3+ toxicity are 56.7 +/- 5% and 21 +/- 4%, respectively. At multivariate analysis, acute mucositis grade, complementary surgery, primary site and performance status proved to be independent predictive factors of grade 2+ late toxicity with P values of <0.001, 0.009, 0.022 and 0.033, respectively. No effect was found for treatment itself on the incidence of late toxicity, although patients treated with accelerated radiotherapy had a higher probability of confluent mucositis than patients treated with alternating chemoradiotherapy (68% vs 32%, P <0.01). CONCLUSIONS: A substantial proportion of surviving patients develops late complications, although severe irreversible reactions occur in a minority of patients. Acute local toxicity can be used to predict local late toxicity that arises within five years of the end of treatment.

[Clinical postoperative surveillance of colorectal carcinoma]. / Sorveglianza clinica post-operatoria del carcinoma del colon-retto.

Post-operative follow-up after "curative" surgery for patients affected by colon-rectal carcinoma depends upon multiple variables such as type of operation (conservative or wide surgery), adoption of neo-adjuvant or adjuvant treatments (i.e. radiotherapy and/or chemotherapy) to surgery, the availability of anatomo-pathological or biological parameters predictive of unfavourable prognosis. Even though an international agreement on follow-up policy has not still reached, patients with colon-rectum cancer should be intensively (every 6 months) checked in the first 3 years from surgery and every 12 months afterwards. An early detection of asymptomatic pelvic recurrences or abdominal neoplastic progression may help prolong survival of patients and improve their quality of life.

Prolonged complete remission after induction chemotherapy followed by chemoradiation with tomotherapy in metastatic nasopharyngeal cancer.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is uncommon in the Western hemisphere and in Europe. The undifferentiated subtype has a relevant propensity to metastasize systemically, mostly in the skeleton. In patients with distant metastasis at presentation there is no consensus on the most appropriate approach. CASE REPORT: Evaluation of a young patient with initially bony metastatic nasopharyngeal cancer treated with platinum-based induction chemotherapy followed by radiotherapy (performed with Tomotherapy) combined to chemotherapy on primary region with curative intent, and subsequent focal irradiation of the bone metastasis. CONCLUSION: After 27 months from the end of the planned treatment the patient has not shown any late toxicity or complications in the treated areas and is without any evidence of progression. It seems appropriate to treat selected metastatic patients with a radical intent, using induction chemotherapy followed by radical chemoradiotherapy on the primary region and high dose radiation on the metastasis. Moreover, Tomotherapy demonstrated a tolerable grade of acute toxicity without any relevant late complications.