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 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.

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.

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.

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.

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.

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.

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.

Image guided hypofractionated radiotherapy by helical tomotherapy for prostate carcinoma: toxicity and impact on Nadir PSA.

AIM: To evaluate the toxicity of a hypofractionated schedule for primary radiotherapy (RT) of prostate cancer as well as the value of the nadir PSA (nPSA) and time to nadir PSA (tnPSA) as surrogate efficacy of treatment. MATERIAL AND METHODS: Eighty patients underwent hypofractionated schedule by Helical Tomotherapy (HT). A dose of 70.2 Gy was administered in 27 daily fractions of 2.6 Gy. Acute and late toxicities were graded on the RTOG/EORTC scales. The nPSA and the tnPSA for patients treated with exclusive RT were compared to an equal cohort of 20 patients treated with conventional fractionation and standard conformal radiotherapy. RESULTS: Most of patients (83%) did not develop acute gastrointestinal (GI) toxicity and 50% did not present genitourinary (GU) toxicity. After a median follow-up of 36 months only grade 1 of GU and GI was reported in 6 and 3 patients as late toxicity. Average tnPSA was 30 months. The median value of nPSA after exclusive RT with HT was 0.28 ng/mL and was significantly lower than the median nPSA (0.67 ng/mL) of the conventionally treated cohort (P = 0.02). CONCLUSIONS: Hypofractionated RT schedule with HT for prostate cancer treatment reports very low toxicity and reaches a low level of nPSA that might correlate with good outcomes.

Stereotactic Ablative Radiotherapy for stage I histologically proven non-small cell lung cancer: an Italian multicenter observational study.

OBJECTIVES: Aim of this retrospective multicenter observational study was to provide data on outcomes and prognostic factors in patients affected with stage I histologically confirmed NSCLC treated with Stereotactic Ablative Radiotherapy (SABR, or Stereotactic Body Radiotherapy, SBRT) outside clinical trials. MATERIALS AND METHODS: We analyzed a cohort of 196 patients with histological/cytological diagnosis of NSCLC. Median age at treatment was 75 years old; median tumor diameter was 2.48 cm, and median GTV 13.3 cc. One hundred fifty-five patients had stage IA disease (79.1%) and 41 patients stage IB disease (20.9%). Total doses ranged from 48 to 60 Gy in 3-8 fractions. Primary endpoints of the study were safety (acute and late toxicity) and efficacy (Local Control, Disease-Free Survival, Overall and Cancer-Specific Survival). RESULTS: Median follow-up time was 30 months. The percentage of grade ≥2 pulmonary toxicity was 3%, and the 30 and 60 days mortality rate was 0%. Local Recurrence-Free Survival was 89.7% at 3 years. Fifty-nine patients (30.1%) had at least one failure (local and/or nodal and/or distant), with a Disease-Free Survival (DFS) rate at 3 years of 65.5%. Overall Survival (OS) and Cancer-Specific Survival (CSS) rates were 68% and 82.1% at 3 years, respectively. Median time to any recurrence was 15 months, while median overall survival time was 54 months. At multivariate analysis, stage IB was the only variable associated to a decrease in DFS, OS and CSS (HR 2.77, p = 0.006; HR 2.38, p = 0.009; HR 4.06, p ≤ 0.001, respectively). A difference in survival according to stage was also evident at the log-rank test (p ≤ 0.0001 for CSS and OS). CONCLUSION: The results of the present study support the routine use of SABR for stage I NSCLC in a daily practice environment. The only prognostic factor that has been confirmed by our analysis was tumor stage (IA vs. IB).

Ablative or palliative stereotactic body radiotherapy with helical tomotherapy for primary or metastatic lung tumor.

AIM: To evaluate the feasibility and outcomes of stereotactic body radiotherapy (SBRT) by helical tomotherapy (HT) for patients with primary or secondary lung cancer. PATIENTS AND METHODS: Between March 2009 and January 2012, 56 patients were selected as candidates for the study and were divided into two subgroups. The ablative SBRT group included 27 patients with T1-T2 non-small cell lung cancer who received four to five large-dose fractions in two weeks and the palliative SBRT group included 29 patients with lung metastases treated with eight lower-dose fractions in four weeks. RESULTS: No differences in acute toxicities were found between different fractionation schemes with different overall treatment times. Actuarial local control at 24 months was better for the ablative group (69.6%) than for the palliative one (40.4%) (p=0.0019). CONCLUSION: HT-based SBRT was feasible and well-tolerated. Local control was satisfactory for patients treated with ablative SBRT but unsatisfactory for those treated with palliative SBRT. Outcomes also suggest the use of ablative SBRT fractionation for palliative intent.

Feasibility of helical tomotherapy for radical dose retreatment in pelvic area: a report of 4 cases.

AIMS AND BACKGROUND: To retrospectively determine acute toxicity and local control in patients with recurrence after definitive radiotherapy for prostate, bladder and rectal carcinoma. METHODS: Between September 2009 and March 2010, 4 patients with a prior history of pelvic radiotherapy were treated with helical tomotherapy. The prior course of radiotherapy was given for prostate cancer in 2 patients, bladder carcinoma in 1 patient and rectal carcinoma in 1 patient. The median prescribed dose of the prior course of radiotherapy was 6320 cGy (range, 5000-7600), and the median elapsed time between the first and second course was 17 months (range, 4-73). The total prescribed dose for tomotherapy retreatment was 60 Gy in 3 patients and 50 Gy in 1 patient. Hormone therapy was administered to 2 patients before and during radiation. No patient underwent surgical resection. RESULTS: The cumulative mean dose to the rectum ranged from 3813 to 6058 cGy; cumulative rectal maximum dose to 1 cc ranged from 6475 to 8780 cGy. Regarding the bladder, the cumulative mean dose was between 4384 and 7612 cGy; cumulative maximum dose to 1 cc ranged from 7560 to 9790 cGy. All patients completed the re-irradiation course. Acute genitourinary toxicity (RTOG scale) was grade 0 in 3 patients and grade 1 in 1 patient; acute gastrointestinal toxicity was grade 0 in 3 patients and grade 1 in 1 patient. With a median follow-up of 9 months (range, 7-12), late toxicity was G0 in all patients. Three patients showed partial response with computed tomography or magnetic resonance imaging, and 1 had a PSA decrease. CONCLUSIONS: Re-irradiation with helical tomotherapy was well tolerated, with low rates of acute and late toxicity. It can be therefore considered a useful tool to improve local control in patients previously treated with radiotherapy. However, a larger number of patients and a longer follow-up are required to assess retreatment safety.

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.

Does treatment of the pelvic nodes with IMRT increase late rectal toxicity over conformal prostate-only radiotherapy to 76 Gy?

PURPOSE: To compare late rectal toxicity rates after three-dimensional conformal radiotherapy to the prostate alone (P-3D-CRT) and whole-pelvis intensity-modulated radiotherapy along with a prostate boost (WP-IMRT/PB) to the same nominal total dose to the prostate. PATIENTS AND METHODS: 68 patients treated with conformal radiotherapy to the prostate only to 76 Gy at the National Institute for Cancer Research, Genoa, Italy, represented the first group (P-3D-CRT). The second group consisted of 45 patients treated at the University of Texas Medical Branch (UTMB), Galveston, TX, USA, with IMRT covering the pelvic nodes and seminal vesicles to 54 Gy at 1.8 Gy per fraction and the prostate to 60 Gy in the same 30 fractions. A separate phase boosted the prostate to 76 Gy (WP-IMRT/PB). Major aspects of planning were remarkably similar at both institutions leaving the inclusion or not of pelvic nodes as the main treatment-related difference between the two groups. Late rectal toxicity was prospectively scored according to the RTOG scale. All patients have a 12-month minimum follow-up, and mean follow-up, similar in both groups, is 25.9 months (SD [standard deviation]: 8.4 months). RESULTS: At 2 years, the estimated cumulative incidence of grade 2 late rectal toxicity is 6%+/-4% for WP-IMRT/PB and 21.2%+/-6% for P-3D-CRT (p=0.06). The difference became significant (HR [hazard ratio]=0.1, 95% CI [confidence interval]: 0.0-0.6; p=0.01) at multivariate analysis. None of the patients developed grade 3+ toxicity. CONCLUSION: Despite the larger treated volume, WP-IMRT/PB allows more rectal sparing than P-3D-CRT.

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.

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.

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.

Anatomic variations due to radical prostatectomy. Impact on target volume definition and dose-volume parameters of rectum and bladder.

BACKGROUND AND PURPOSE: A quantitative estimate of the impact of prostatectomy on pelvic anatomy is unavailable, even if it would be an important prerequisite for a precise definition of clinical target volume (CTV) in post-prostatectomy radiotherapy. The purpose of this study was to investigate the impact of prostatectomy on the definition of CTV, on the position of bladder and rectum and their implications for three-dimensional conformal radiotherapy (3-D CRT). PATIENTS AND METHODS: Six patients eligible for radical retropubic prostatectomy were considered. Each patient underwent a planning CT between 1 week and 1 month before surgery (CTpre), and then CT was repeated in the same positioning 1-2 months after surgery (CTpost). For each patient the CT(pre/post) scans were matched; rectum, bladder and CTV were contoured on both CT scans for each patient by one observer. Two different CTVs were contoured: CTV1: prostate + seminal vesicles in CTpre; prostate + seminal vesicles surgical bed in CTpost; CTV2: prostate in CTpre; prostate surgical bed in CT(post). After image registration, the contours of rectum, bladder and CTV1/2 drawn on CTpost were transferred on CTpre. The corresponding planning target volumes (PTVs) were generated, and for each PTV, a conformal four field technique using 18-MV X-rays was planned. The volumes of CTV1, CTV2, PTV1, PTV2, rectum and bladder pre- and post-surgery were compared. Differences in 3-D position of these structures before and after surgery were analyzed by beam's eye view (BEV) images. Pre- and post-surgery dose-volume histograms (DVHs) of rectum and bladder were compared together with the fraction of rectum/bladder receiving at least 95% of the ICRU dose (V95), the treated volume (TV, body included in the 95% isodose) and the irradiated volume (IV, body included in the 50% isodose). RESULTS: For both CTV1 and CTV2, the volumes were significantly reduced after prostatectomy (average reduction around 30 cm3 for both; range 0-60 cm3). This reduction was mainly due to a more caudal definition of the cranial edge of CTV after prostatectomy (average difference for CTV2: 1.5 cm; range 0-2.5 cm). Concerning the bladder, a systematic posterior shift of the bladder base (average: 1.5 cm) was found and was correlated with a significant reduction of V95 for bladder (around 10 cm3; p = 0.03). V95 of the rectum, TV and IV also resulted to be significantly lower after surgery. The average reduction of V95 for the rectum was relatively small (2.5 cm3 of rectal wall). CONCLUSION: The impact of prostatectomy on CTV definition is high. A significant reduction of CTV, PTV, TV and IV may be expected after surgery with a consequent reduction of the portions of rectum/bladder irradiated with adjuvant radiotherapy.