Radioprotective effect of calcium channel blockers against late rectal bleeding in prostate cancer.

OBJECTIVE: This study was done to assess the impact of clinical factors and in particular the use of drugs for concomitant illnesses on late radiation-induced rectal bleeding in patients with prostate cancer. MATERIALS AND METHODS: Patients with histologically proven prostate adenocarcinoma treated with radical radiotherapy and followed up for at least 6 months were selected. The correlation between late rectal bleeding and a number of factors was investigated by univariate and multivariate analysis. RESULTS: A total of 278 patients who underwent radiotherapy at our institution between October 2002 and May 2011 were selected. At univariate analysis, delivery of radiation doses higher than 70 Gy and use of angiotensin-converting enzyme inhibitors were associated with a higher incidence of rectal bleeding. Conversely, patients who used calcium channel blockers had a lower risk (3-year rectal bleeding-free survival 89.8 versus 66.5 %, p = 0.043). At multivariate analysis, use of calcium channel blockers was found to have a protective effect with a hazard ratio of 0.3 (95 % CI 0.12-0.96). Delivery of higher radiation doses was associated with an increased risk of rectal bleeding (hazard ratio 3.02, 95 % CI 1.23-7.38). CONCLUSIONS: Use of calcium channel blockers during and after radiotherapy treatment might have a protective effect against late rectal bleeding. If these results are reconfirmed by larger clinical series, calcium channel blockers may be tested as radioprotector agents in clinical trials.

Quality of life and toxicity of stereotactic radiotherapy in pancreatic tumors: a case series.

AIM: To analyze the results of extracranial stereotactic radiotherapy (ESRT) experience in pancreatic cancer patients. METHODS: Four noncoplanar fixed beams were used in all patients. RESULTS: Analysis of 16 patients was carried out. Overall response rate was 56.2%. Fifteen patients experienced local and/or distant progression of disease (median follow-up: 24 months). Two-year local progression-free, distant progression-free, and overall survivals were 85.7%, 58.7%, and 50.0%, respectively. Toxicity was less than grade 2 in all, although 1 patient had severe duodenal bleeding. Quality of life scores were unchanged. CONCLUSIONS: ESRT was associated with low complication rate, and not worsening the patients' quality of life.

Concomitant boost plus large-field preoperative chemoradiation in locally advanced uterine cervix carcinoma: Phase II clinical trial final results (LARA-CC-1).

OBJECTIVE: To report the Phase II study final results in terms of pathological complete response (pCR) and complications in locally advanced cervical carcinoma (LACC) patients treated with chemoradiation (CT/RT) regimen based on accelerated fractionation, nodal extended fields and adjuvant radical surgery. METHODS: The sample size was quantified according to published data which shows that CT/RT followed by radical surgery in LACC patients provides a pCR rate above 45%. The 2-stage design by Simon was used to test the null hypothesis that the true pCR would improve by above 20%. The chemoradiation regimen was considered active if >24/43 pCRs were recorded. 40 Gy/2 Gy fraction in 4 weeks was delivered to nodal volume extending up to L3 vertebra, concurrently with chemotherapy. 45 Gy in 20 fractions with a concomitant boost strategy was delivered to the macroscopic disease only. RESULTS: 47 patients were enrolled. Median follow-up was 26 months (3-52 months). Pathological response was assessed in 44/47 patients: 17/44 (38.6%) showed a pCR to treatment, and 9/44 cases (20.5%) showed microscopic disease. Pelvic nodal metastases were documented in 9/44 cases (20.5%). 87.5% of recurrences were extra pelvic. Five patients (11%) developed acute severe gastrointestinal toxicity. The actuarial cumulative 2-year incidence of G ≥ 2 late cutaneous, gastrointestinal, and genitourinary toxicity was 10.3%, 8.3% and 24.9%, respectively. The 3-year DFS was 77.1%, while the 3-year OS was 80.5%. CONCLUSIONS: Our results confirm the high tolerability and efficacy of this accelerated regimen. However, based on the study design, 45 Gy as a concomitant boost CT/RT delivered by a 3D technique does not seem sufficient to increase pCR rate.

3D conformal postoperative radiotherapy with concomitant boost in uterine cancer: results of a phase I-II study (ADA-RT-1).

OBJECTIVE: A phase I-II prospective clinical trial of adjuvant accelerated radiation therapy (ADA-RT-1 trial) was set up in order to investigate the feasibility and efficacy of a pelvic conformal radiotherapy technique with concomitant boost (CB technique) to the vaginal vault in high-risk uterine cancers. METHODS: Patients with uterine (endometrial cancer and sarcomas) and cervical neoplasm received external radiotherapy delivered in a short overall treatment time with a CB technique. The prescribed radiotherapy doses were 45/1.8 Gy/fraction to the pelvis and 55/2.2 Gy/fraction to the upper two-thirds of vagina plus resection lines in the parametria, respectively; treatment was administered in 25 fractions along 5 weeks. RESULTS: This study included 91 consecutive gynecological cancer patients (endometrial=72; cervical=10; sarcoma=9; median follow-up: 25 months, range: 5-72 months). Acute toxicity requiring treatment interruption (≥grade 3) was observed in 7 patients (7.7%). No case of vaginal recurrence was documented. Actuarial 3-year loco-regional control rate was 97.7%, whereas 3-year disease-free survival and overall survival rates were 88.5% and 94.0%, respectively. CONCLUSION: In summary, the CB technique provides a high probability of local control with acceptable toxicity and shortening of the overall treatment time; moreover, it may offer some advantages to resource constrained medical environments.

Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: results of a phase II study.

BACKGROUND: An intensified multidrug chemotherapy regimen (raltitrexed plus oxaliplatin, Tom-Ox) plus concomitant boost radiotherapy, in the neoadjuvant treatment of locally advanced rectal cancer patients, was shown feasible in our previous study. The aim of this study was to evaluate the efficacy in terms of pathologic complete response to pre-operative therapy. MATERIAL AND METHODS: A Phase II study was designed and clinical stage T3-T4 and/ or N ≥ 1 patients were treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in terms of clinical and pathologic response to pre-operative therapy. According to the Gehan's design study, 25 patients were enrolled. Toxicity was assessed according to the RTOG-EORTC and CTCAE v.3.0 criteria. RESULTS: Twenty-five consecutive patients were treated. Twenty-two of the 25 (88%) patients had a partial clinical response at the time of pre-operative magnetic resonance imaging (MRI). Only one patient showed progressive systemic disease at pre-surgical revaluation and was subjected only to biopsy to evaluate pathological response. Twenty-four patients (96%) underwent surgery. Overall, pathologic complete response was observed in eight patients (32%; CI 0.95:12-55%) and only microscopic tumor foci (pTmic) in two patients (pT0-mic: 40%; CI 0.95:18-63%). Nineteen patients (76%) showed tumor down-staging. Proctitis and/or diarrhea were the most frequent acute side effects experienced. Eighteen patients had grade 1-2 toxicity (77%); whereas two patients experienced grade 3 toxicity (8%). Two-year Local control and actuarial Disease Free Survival were 100% and 91%, respectively. CONCLUSION. An intensified regimen of concomitant boost radiotherapy plus concurrent raltitrexed and oxaliplatin, can be safely administered in patients with locally advanced rectal cancer. This regimen produces high rates of pathological complete response. Based on available data, this type of treatment could be offered to patients with more advanced tumors (T4 or local recurrence).

Forward planned intensity modulated radiotherapy (IMRT) for whole breast postoperative radiotherapy. Is it useful? When?

The purpose was to compare the dosimetric results observed in 201 breast cancer patients submitted to tangential forward intensity-modulated radiation therapy (IMRT) with those observed in 131 patients treated with a standard wedged 3D technique for postoperative treatment of whole breast, according to breast size and supraclavicular node irradiation. Following dosimetric parameters were used for the comparison: D(max), D(min), D(mean), V(95%) and V(107%) for the irradiated volume; D(max), D(mean), V(80%) and V(95%) for the ipsilateral lung; D(max), D(mean), V(80%) and V(95%) for the heart. Stratification was made according to breast size and supraclavicular (SCV) nodal irradiation. As respect to irradiated volume, a significant reduction of V(107%) (mean values: 7.0 ± 6.6 versus 2.4 ± 3.7, p < 0.001) and D(max) (mean % values: 111.2 ± 2.7 versus 107.7 ± 6.3, p < 0.001), and an increase of D(min) (mean % values: 65.0 ± 17.4 versus 74.9 ± 12.9, p < 0.001) were observed with forward IMRT. The homogeneity of dose distribution to target volume significantly improved with forward IMRT in all patient groups, irrespective of breast size or supraclavicular nodal irradiation. When patients treated with supraclavicular nodal irradiation were excluded from the analysis, forward IMRT slightly reduced V(80%) (mean values: 3.7 ± 2.6 versus 3.0 ± 2.4, p = 0.03) and V(95%) (mean values 1.9 ± 1.8 versus 1.2%± 1.5; p = 0.001) of the ipsilateral lung. The dose to the heart tended to be lower with IMRT but this difference was not statistically significant. Tangential forward IMRT in postoperative treatment of whole breast improved dosimetric parameters in terms of homogeneity of dose distribution to the target in a large sample of patients, independent of breast size or supraclavicular nodal irradiation. Lung irradiation was slightly reduced in patients not undergoing to supraclavicular irradiation.

A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer.

PURPOSE: The objective of this study was to determine the effect on resection rate and survival of neoadjuvant chemoradiotherapy for primarily unresectable locally advanced pancreatic carcinoma. METHODS: A systematic review of recently published literature was performed. Resection rates and survival data were derived from reports published from 2000 onwards. Only recent studies, based on radiotherapy with standard dose and fractionation, have been analyzed. RESULTS: Thirteen studies with a total of 510 patients met selection criteria. A resection rate of 8.3-64.2% was reported (median, 26.5%). Of the operated patients, 57.1-100% (median, 87.5%) had R0 tumor resection. Most papers reported occasional pathological complete responses (CR, 3.0-8.8%). When outcome in all patients was considered, median survival ranged from 9 to 23 (median, 13.3) months, comparing favorably with literature data based on concurrent chemoradiation alone (range, 8.6-13 months). Surprisingly, in patients with unresectable tumor at presentation, median survival after surgery ranged from 16.4 to 32.3 (median, 23.6) months. CONCLUSIONS: The finding of a high proportion of R0 resection among all resections performed confirms the activity of neoadjuvant radiochemotherapy and should not be neglected. Based on these data, patients with unresectable pancreatic cancer without disease progression after chemoradiotherapy should be considered for radical surgery.

Single-arm phase II study of conformal radiation therapy and temozolomide plus fractionated stereotactic conformal boost in high-grade gliomas: final report.

PURPOSE: To assess survival, local control and toxicity using fractionated stereotactic conformal radiotherapy (FSCRT) boost and temozolomide in high-grade gliomas (HGGs). PATIENTS AND METHODS: Patients affected by HGG, with a CTV(1)(clinical target volume, representing tumor bed ± residual tumor + a margin of 5 mm) ≤ 8 cm were enrolled into this phase II study. Radiotherapy (RT, total dose 6,940 cGy) was administered using a combination of two different techniques: three-dimensional conformal radiotherapy (3D-CRT, to achieve a dose of 5,040 or 5,940 cGy) and FSCRT boost (19 or 10 Gy) tailored by CTV(1)diameter (≤ 6 cm and > 6 cm, respectively). Temozolomide (75 mg/m(2)) was administered during the first 2 or 4 weeks of RT. After the end of RT, temozolomide (150-200 mg/m(2)) was administered for at least six cycles. The sample size of 41 patients was assessed by the single proportion-powered analysis. RESULTS: 41 patients (36 with glioblastoma multiforme [GBM] and five with anaplastic astrocytoma [AA]) were enrolled; RTOG neurological toxicities G1-2 and G3 were 12% and 3%, respectively. Two cases of radionecrosis were observed. At a median follow-up of 44 months (range 6-56 months), global and GBM median overall survival (OS) were 30 and 28 months. The 2-year survival rate was significantly better compared to the standard treatment (63% vs. 26.5%; p < 0.00001). Median progression-free survival (PFS) was 11 months, in GBM patients 10 months. CONCLUSION: FSCRT boost plus temozolomide is well tolerated and seems to increase survival compared to the standard treatment in patients with HGG.

Concomitant boost dose escalation plus large-field preoperative chemoradiation in locally advanced carcinoma of the uterine cervix: results of a phase I study (LARA-CC-1).

OBJECTIVE: To determine the recommended preoperative dose of large-field chemoradiation along with concomitant boost dose escalation on the tumor in locally advanced cervical carcinoma (LACC). PATIENTS AND METHODS: A radiation dose of 40Gy over four weeks, 2Gy per fraction, was delivered to the tumor and the lymphatic drainage (planning target volume, PTV2), which encompassed a volume larger than standard (upper field border: L3 vertebra), concurrently with chemotherapy (cisplatin and 5-fluorouracil). Radiation dose was escalated to the macroscopic tumor only (PTV1) with a concomitant boost strategy. Three dose levels were planned: levels 1 (no PTV1 boost), 2 (45/2.25Gy) and 3 (50/2.5Gy). Patients were treated in cohorts of six to twelve per group using a standard phase I study design. The recommended dose was exceeded if >2 of 6 patients in a cohort experienced dose-limiting toxicity (DLT). RESULTS: 32 patients (median age: 50 years; FIGO stage IB2: 4, IIA: 3, IIB: 21, III-IVA: 4) were enrolled. Median follow-up was 18 months (3-49 months). The most common grade 3/4 toxicity was gastrointestinal (diarrhea). Since three DLTs (grade 3 diarrhea, n=2; grade 3 proctitis, n=1), were observed in 4 patients at level 3, the trial was closed and level 2 was judged as the recommended dose. CONCLUSION: Based on the data from this phase I study, 45Gy/2.25Gy to macroscopic tumor and 40Gy/2Gy to lymphatic drainage may be considered the recommended doses.

Radiotherapy and concomitant temozolomide during the first and last weeks in high grade gliomas: long-term analysis of a phase II study.

We tested the efficacy and safety of temozolomide (TMZ) when given concomitantly to radiotherapy only in the first and last weeks of treatment to patients affected by high grade gliomas. Conformal radiotherapy (CTV1: tumor bed + residual tumor if present + 1.5 cm, 5,940 cGy, 180 cGy/day; CTV2: oedema, 3,960 cGy, 180 cGy/day) was associated with TMZ, 75 mg/m(2) x 5 days, the first and last weeks of radiotherapy. Adjuvant chemotherapy with TMZ (150 mg/mq daily x 5 days, q28 on the first cycle, 200 mg/mq daily x 5 days, q28 for the following cycles) was given, after chemoradiation, until disease progression or up to 6 cycles. From October 2000 to December 2003, 29 patients (25 GBL, 86.2%; 4 AA, 13.8%) were enrolled in this study. Twenty-two patients (75.8%) received a median 6 cycles of adjuvant chemotherapy with TMZ (range 1-20). Hematological toxicity was absent during concomitant chemoradiation and mild in adjuvant therapy, while neurological toxicity (seizures) was observed only in one case. At a median follow-up of 66 months (range 3-96), median progression-free survival (PFS) was 8 months, with a 1- and 2-year PFS of 46.7 and 28.7%, respectively; median overall survival (OS) time was 21 months, with a 1- and 2-year OS of 69.2 and 42.3%, respectively. In our experience, TMZ proved to be effective even when given only during the first and the last week of radiotherapy, with lower hematological toxicity.

Capecitabine based postoperative accelerated chemoradiation of pancreatic carcinoma. A dose-escalation study.

UNLABELLED: The objective of this study was to evaluate the safety of escalating up to 55 Gy within five weeks, the dose of external beam radiotherapy to the previous tumor site concurrently with a fixed daily dose of capecitabine, in patients with resected pancreatic cancer. MATERIAL AND METHODS: Patients with resected pancreatic carcinoma were eligible for this study. Capecitabine was administered at a daily dose of 1600 mg/m (2). Regional lymph nodes received a total radiation dose of 45 Gy with 1.8 Gy per fractions. The starting radiation dose to the tumor bed was 50.0 Gy (2.0 Gy/fraction, 25 fractions). Escalation was achieved up to a total dose of 55.0 Gy by increasing the fraction size by 0.2 Gy (2.2 Gy/fraction), while keeping the duration of radiotherapy to five weeks (25 fractions). A concomitant boost technique was used. Dose limiting toxicity (DLT) was defined as any grade>3 hematologic toxicity, grade>2 liver, renal, neurologic, gastrointestinal, or skin toxicity, by RTOG criteria, or any toxicity producing prolonged (> 10 days) radiotherapy interruption. RESULTS AND DISCUSSION: Twelve patients entered the study (median age: 64 years). In the first cohort (six patients), no patient experienced DLT. Similarly in the second cohort, no DLT occurred. All 12 patients completed the planned regimen of therapy. Nine patients experienced grade 1-2 nausea and/or vomiting. Grade 2 hematological toxicity occurred in four patients. The results of our study indicate that a total radiation dose up to 55.0 Gy/5 weeks can be safely administered to the tumor bed, concurrently with capecitabine (1600 mg/m (2)) in patients with resected pancreatic carcinoma.

Active Breathing Coordinator in adjuvant three-dimensional conformal radiotherapy of early stage breast cancer: a feasibility study.

AIMS: To investigate the technical feasibility of utilizing the Active Breathing Coordinator for planning of postoperative three-dimensional conformal radiation therapy in patients with early stage breast cancer undergoing breast conservation therapy. METHODS: Patients with early stage breast cancer for whom adjuvant radiotherapy after breast-conserving surgery was planned were consecutively enrolled. Five sessions of simulation with the Active Breathing Coordinator were planned for each patient. Computed tomography for simulation was not acquired until a good level of compliance with the procedure was achieved by the patient. Patients who did not show a satisfactory level of compliance after the planned fifth session were defined as noncompliant. Two simulation computed tomography scans were acquired: the first without the Active Breathing Coordinator during free breathing, the second with the Active Breathing Coordinator. Forward intensity-modulated treatment plans were calculated. Mean lung dose (MLDipsilateral) and V30 (V30lung) for the ipsilateral lung and V30 for the heart (V30heart), were evaluated. RESULTS: Twenty consecutive patients were enrolled (6 with left-sided breast cancer and 14 with right-sided breast cancer). Eighteen of the patients completed the simulation computed tomography with the Active Breathing Coordinator after 1-5 sessions (median, 3). In 16 of the 18 patients, a reduction of V301ung was observed with the Active Breathing Coordinator. In 15 of the 18 patients, a reduction of MLDipsiateral was also observed. In 5 of the 6 patients with left-sided breast cancer, a reduction of V30heart was noted. CONCLUSIONS: Routine application of the Active Breathing Coordinator in clinical practice is feasible, even though it requires an increased workload. Dosimetric results are encouraging in terms of a better sparing of the ipsilateral lung and the heart.

Phase I-II studies on accelerated IMRT in breast carcinoma: technical comparison and acute toxicity in 332 patients.

BACKGROUND AND PURPOSE: To evaluate the results in terms of dosimetric parameters and acute toxicity of two clinical studies (MARA-1 and MARA-2) on accelerated IMRT-based postoperative radiotherapy. These results are compared with historical control group (CG) of patients treated with "standard" 3D postoperative radiotherapy. MATERIALS AND METHODS: Prescribed dose to the breast was 50.4Gy in the CG, 40Gy in MARA-1 (low risk of local recurrence), and 50Gy in MARA-2 (medium-high risk of recurrence). The tumor bed total dose was 60.4Gy (sequential 10Gy electron boost), 44Gy (concomitant 4Gy boost), and 60Gy (concomitant 10Gy boost) in CG, MARA-1 and MARA-2 studies, respectively. Overall treatment time was of 32 fractions for CG (6.4weeks); 16 fractions for MARA-1 study (3.2weeks) and 25 fractions for MARA-2 study (5weeks). RESULTS: Three hundred and thirty two patients were included in the analysis. Dosimetric analysis showed D(max) and V(107%) reduction (p<0.001) and D(min) improvement (p<0.001) in the PTV in patients treated with IMRT. Grade 2 acute skin toxicity was 33.6%, 13.1%, and 45.1% in the CG, MARA-1, and MARA-2, respectively (p<0.001), and grade 3 acute skin toxicity was 3.1%, 1.0%, and 2.0%, respectively. Similarly, larger PTV and use of chemotherapy with anthracyclines and taxanes were associated with a greater acute toxicity. With a median follow-up of 31 months, no patients showed local or nodal relapse. CONCLUSIONS: A simplified step and shoot IMRT technique allowed better PTV coverage and reduced overall treatment time (CG, 6.6weeks; MARA-1, 3.2weeks; MARA-2, 5weeks) with acceptable short-term toxicity.

Stereotactic radiotherapy in recurrent gynecological cancer: a case series.

Scarce data are available on the use of extracranial stereotactic radiotherapy in recurrent gynecological tumors. The aim of this report was to analyze the results of our preliminary experience with extracranial stereotactic radiotherapy in locally or distantly recurrent gynecological tumors. Extracranial stereotactic radiotherapy was planned by the Precise-Plan treatment planning system. Patients were immobilized using the Stereotactic Body-Frame. Five consecutive daily fractions were delivered; dose/fraction and total dose were defined based on an institutional dose-escalation protocol. A class solution with 4 non-coplanar fixed beams based on the tetrad configuration was used in all patients. Eleven patients (12 lesions), were included in the analysis. Stereotactic radiotherapy was delivered as first radiotherapy treatment (5 patients), or as retreatment (6 patients). Complete clinical response was achieved in 8/12 lesions (66.6%), while partial response was documented in 2/12 lesions (16.6%). With a median follow-up of 19 months (range, 2-37 months), 7 patients (63%) experienced local and/or distant progression of disease. The 2-year local progression-free survival was 81.8%, while the 2-year metastases-free survival was 54.4%. The 2-year overall survival was 63.6%. Acute and late toxicities were grade 2 or less. There was no difference in quality of life scores between the data collected before extracranial stereotactic radiotherapy and at first follow-up evaluation. Fractionated extracranial stereotactic radiotherapy administered up to a dose of 30 Gy in five fractions is well tolerated. Further studies of extracranial stereotactic radiotherapy and novel radiotherapy techniques are warranted in the challenging setting of recurrent gynecological tumors.

Intraoperative radiation therapy in resected pancreatic carcinoma: long-term analysis.

PURPOSE: The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT+IORT). METHODS AND MATERIALS: From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative "flash" RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996-1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. RESULTS: Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter (p=0.019). CONCLUSIONS: The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT (approximately 50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT+external RT).

Novel prognostic groups in thymic epithelial tumors: assessment of risk and therapeutic strategy selection.

PURPOSE: To assess the role of multimodality treatment on patients with thymic epithelial tumors (TETs) (i.e., thymomas and thymic squamous cell carcinoma) and to define the prognostic classes according to the Masaoka and World Health Organization histologic classification systems. METHODS AND MATERIALS: Primary surgery was the mainstay of therapy. Extended thymectomy was performed in all cases. The cases were primarily staged according to the Masaoka system. Adjuvant radiotherapy was given to patients diagnosed with Masaoka Stage II, III, and IVA TET. Adjuvant chemotherapy was administered in selected cases. RESULTS: We reviewed the records of 120 patients with TETs, with a mean follow-up of 13.8 years. Of the 120 patients, 98 (81.6%) received adjuvant radiotherapy. Of these 98 patients, Grade 1-2 pulmonary or esophageal toxicity was acute in 12 (12.2%) and late in 8 (8.2%). The median overall survival was 21.6 years. Of the 120 patients, 106 were rediagnosed and reclassified according to the World Health Organization system, and the survival rate was correlated with it. Three different prognostic classes were defined: favorable, Masaoka Stage I and histologic grade A, AB, B1, B2 or Masaoka Stage II and histologic grade A, AB, B1; unfavorable, Stage IV disease or histologic grade C or Stage III and histologic grade B3; intermediate, all other combinations. The 10- and 20-year survival rate was 95% and 81% for the favorable group, 90% and 65% for the intermediate group, and 50% and 0% for the unfavorable group, respectively. Local recurrence, distant recurrence, and tumor-related deaths were also evaluated. CONCLUSION: The analysis of our experience singled out three novel prognostic classes and the assessment of risk identified treatment selection criteria.

Complexity index (COMIX) and not type of treatment predicts undetected errors in radiotherapy planning and delivery.

BACKGROUND AND PURPOSE: Quality assurance procedures (QA) may reduce the risk of errors in radiotherapy. The aim of this study was to assess a QA program based on independent check (IC) procedures in patients undergoing 3D, intensity modulated (IMRT) and extracranial stereotactic (ESRT) radiotherapy. MATERIALS AND METHODS: IC for set-up (IC1) and for radiotherapy treatments (IC2) was tested on 622 patients over a year. Fifteen events/parameters and 17 parameters were verified by IC1 and IC2, respectively. A third evaluation check (IC3) was performed before treatment. Potential errors were classified based on their magnitude. Incidents involving only incorrect or incomplete documentation were segregated. Treatments were classified based on a complexity index (COMIX). RESULTS: With IC1, 75 documentation incidents and 31 potential errors were checked, and with IC2 111 documentation incidents and 6 potential errors were checked. During the study period 10 errors undetected by standard procedures (IC1, IC2) were detected by chance or by IC3. The incidence of errors and serious errors undetected by standard procedures was 1.6% and 0.6%, respectively. There was no higher incidence of errors undetected in patients undergoing IMRT or ESRT, while there was a higher incidence of errors undetected in more complex treatments (p < 0.001). CONCLUSIONS: Systematic QA procedures can reduce the risk of errors. The risk of errors undetected by standard procedures is not correlated with the treatment technological level (3D versus IMRT/ESRT).

Videoconferencing to enhance the integration between clinical medicine and teaching: a feasibility study.

AIMS AND BACKGROUND: The aim of the study was to analyze the feasibility of a setting up of a radiotherapy department using videoconferencing technology. MATERIAL AND METHODS: A videoconferencing network was started to link an academic center of radiotherapy to a peripheral center of research at the start of its activity. Two years of data of involved professionals, subjects of links, audio, video link problems and running costs were recorded. RESULTS: A total of 418 links was established for an overall duration of 458 hours. The participants included all departmental staff. Videoconferencing involved teaching, ward organization, medical care and scientific subjects. In the second year ofexperience, the number of videoconferencing links was higher than the first (232 vs 186). Link times were reasonable for both skilled and unskilled operators. Overall, the cost per minute of link was 0.2 Euro, and the mean cost per link was 13 Euros. Videoconferencing was integrated with fax and computer networks to enhance sharing paper and electronic documents. Audio-video technical problems progressively decreased: the link was definitively interrupted or its activation unfeasible in only 1.0% of cases. CONCLUSIONS: Our experience suggests that the establishment of a link between radiotherapy departments addressed to these aims is feasible by a videoconferencing network.

Squamous cell carcinoma antigen in follow-up of cervical cancer treated with radiotherapy: evaluation of cost-effectiveness.

PURPOSE: The squamous cell carcinoma (SCC) antigen is still considered the most accurate serologic tumor marker in cervical carcinoma. We assessed the contribution of the SCC assay to the detection of recurrences in patients treated with radiotherapy. METHODS AND MATERIALS: The pattern of recurrence and follow-up data were prospectively recorded for 135 patients. Of the 135 patients, 103 (76.3%) had primary cervical carcinoma and 32 (23.7%) had already experienced disease recurrence that had been successfully treated with surgery (n = 2), surgery plus radiotherapy (n = 2), radiotherapy (n = 5), or concomitant chemoradiotherapy (n = 23). The follow-up evaluations (chest X-ray, abdominopelvic magnetic resonance imaging, gynecologic examination with colposcopy, Papanicolaou smear, and SCC assay) were performed at 6-month intervals; the evaluation was done earlier if recurrent disease was suspected. The median follow-up time was 29 months (range, 6-131). The SCC serum levels were assayed, and a cost analysis was done. RESULTS: A total of 481 SCC determinations were performed. Of the 135 patients, 43 (31.8%) experienced disease recurrence. The SCC levels were higher in those with recurrent disease than in the disease-free patients. Elevation of SCC was documented in 34 (79.1% sensitivity) of 43 recurrences before symptoms appeared. Of the 38 patients with serum SCC elevation, 34 developed a recurrence (positive predictive value, 89.5%). Of the 97 patients with negative SCC serum levels, 88 had negative findings at the clinicoradiologic evaluation (negative predictive value, 90.7%). A simplified approach (SCC plus gynecologic examination) was evaluated. Compared with the complete follow-up program, the rate of missed recurrence was 2.2%. The total projected cost per patient for 5 years of follow-up for the simplified procedure was approximately 12.2-fold lower than the standard approach. CONCLUSIONS: Our results have shown that a simplified diagnostic approach, including the SCC assay and gynecologic examination, can detect a high rate of recurrence from cervical cancer, with a very favorable cost-effective profile.

Application of a practical method for the isocenter point in vivo dosimetry by a transit signal.

This work reports the results of the application of a practical method to determine the in vivo dose at the isocenter point, D(iso), of brain thorax and pelvic treatments using a transit signal S(t). The use of a stable detector for the measurement of the signal S(t) (obtained by the x-ray beam transmitted through the patient) reduces many of the disadvantages associated with the use of solid-state detectors positioned on the patient as their periodic recalibration, and their positioning is time consuming. The method makes use of a set of correlation functions, obtained by the ratio between S(t) and the mid-plane dose value, D(m), in standard water-equivalent phantoms, both determined along the beam central axis. The in vivo measurement of D(iso) required the determination of the water-equivalent thickness of the patient along the beam central axis by the treatment planning system that uses the electron densities supplied by calibrated Hounsfield numbers of the computed tomography scanner. This way it is, therefore, possible to compare D(iso) with the stated doses, D(iso,TPS), generally used by the treatment planning system for the determination of the monitor units. The method was applied in five Italian centers that used beams of 6 MV, 10 MV, 15 MV x-rays and (60)Co gamma-rays. In particular, in four centers small ion-chambers were positioned below the patient and used for the S(t) measurement. In only one center, the S(t) signals were obtained directly by the central pixels of an EPID (electronic portal imaging device) equipped with commercial software that enabled its use as a stable detector. In the four centers where an ion-chamber was positioned on the EPID, 60 pelvic treatments were followed for two fields, an anterior-posterior or a posterior-anterior irradiation and a lateral-lateral irradiation. Moreover, ten brain tumors were checked for a lateral-lateral irradiation, and five lung tumors carried out with three irradiations with different gantry angles were followed. One center used the EPID as a detector for the S(t) measurement and five pelvic treatments with six fields (many with oblique incidence) were followed. These last results are reported together with those obtained in the same center during a pilot study on ten pelvic treatments carried out by four orthogonal fields. The tolerance/action levels for every radiotherapy fraction were 4% and 5% for the brain (symmetric inhomogeneities) and thorax/pelvic (asymmetric inhomogeneities) irradiations, respectively. This way the variations between the total measured and prescribed doses at the isocenter point in five fractions were well within 2% for the brain treatment, and 4% for thorax/pelvic treatments. Only 4 out of 90 patients needed new replanning, 2 patients of which needed a new CT scan.