Abdomen Irradiation Research Articles

Whole abdomen irradiation in epithelial ovarian cancer: A single institution study

Background: The examination of the use of whole abdomen irradiation open field technique in optimally debulked patients with no residual disease with epithelial ovarian cancer (OC). Methods: Between 1993 and 2007, 20 patients with optimally cytoreduced epithelial OC were treated with WAI. The stage distribution was stage I in 15 patients, stage II in 1, and stage III in 4. The grade distribution was grade 1 in 10 patients, grade 2 in 4, and grade 3 in 6. WAI consisted of 30 Gy, delivered in daily fractions, mainly of 1.5 Gy (95%), 5 days/weekly, in 14 patients. After abdominal irradiation, in 75% of the patients a pelvic boost, and in 7 a boost to other risk sites was given to reach 45 - 50 Gy. Nine patients received platinum based chemotherapy (CT). Median follow-up was 7.96 years. Results: The overall survival (OS) rate was 82% and 70% at 5 and 10 years. A tendency to better survival was found in patients with age ? 40 than in those with > 40 years (100%:100% vs. 68%:51%; p=0.03). Patients with grade 1-2 tumors had significantly better 5- and 10-year survival rate than those with grade 3 tumors (100%:100% vs. 40%:20%; p<0.00). The 5- and 10-year OS for the patients 'with' and 'without' a pelvic boost turned to be in favor of the patients 'with' the boost (91%:91% vs. 60%:40%; p=0.02). In 15 patients (75%) RT was transiently interrupted because of acute gastrointestinal and hematological toxicity. Neither grade 4 acute complications nor was mortality observed. Late gastrointestinal effect developed in 1 patient, presented with grade 4 complications. The development of second primary malignancy was not observed during the follow-up period. Conclusion: WAI achieves a quite favorable 5- and 10-year survival rate with an acceptable risk of acute and late side effects in properly selected patients with epithelial OC.

Adjuvant whole abdominal intensity modulated radiotherapy (IMRT) for high risk stage FIGO III patients with ovarian cancer (OVAR-IMRT-01) – Pilot trial of a phase I/II study: study protocol

BackgroundThe prognosis for patients with advanced epithelial ovarian cancer remains poor despite aggressive surgical resection and platinum-based chemotherapy. More than 60% of patients will develop recurrent disease, principally intraperitoneal, and die within 5 years. The use of whole abdominal irradiation (WAI) as consolidation therapy would appear to be a logical strategy given its ability to sterilize small tumour volumes. Despite the clinically proven efficacy of whole abdominal irradiation, the use of radiotherapy in ovarian cancer has profoundly decreased mainly due to high treatment-related toxicity. Modern intensity-modulated radiation therapy (IMRT) could allow to spare kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose.Methods/DesignThe OVAR-IMRT-01 study is a single center pilot trial of a phase I/II study. Patients with advanced ovarian cancer stage FIGO III (R1 or R2< 1 cm) after surgical resection and platinum-based chemotherapy will be treated with whole abdomen irradiation as consolidation therapy using intensity modulated radiation therapy (IMRT) to a total dose of 30 Gy in 1.5 Gy fractions. A total of 8 patients will be included in this trial. For treatment planning bone marrow, kidneys, liver, spinal cord, vertebral bodies and pelvic bones are defined as organs at risk. The planning target volume includes the entire peritoneal cavity plus pelvic and para-aortic node regions.DiscussionThe primary endpoint of the study is the evaluation of the feasibility of intensity-modulated WAI and the evaluation of the study protocol. Secondary endpoint is evaluation of the toxicity of intensity modulated WAI before continuing with the phase I/II study. The aim is to explore the potential of IMRT as a new method for WAI to decrease the dose to kidneys, liver, bone marrow while covering the peritoneal cavity with a homogenous dose, and to implement whole abdominal intensity-modulated radiotherapy into the adjuvant multimodal treatment concept of advanced ovarian cancer FIGO stage III.

Gamma-H2AX foci formation in peripheral blood lymphocytes of tumor patients after local radiotherapy to different sites of the body: Dependence on the dose-distribution, irradiated site and time from start of treatment

Purpose: To evaluate the relationship between an estimated integral total body radiation dose delivered and phosphorylated histone H2AX protein (γ-H2AX) foci formation in peripheral blood lymphocytes of cancer patients.Material and methods: γ-H2AX formation was quantified as the mean number of foci per lymphocyte (NmeanH2AX) and the percentage of lymphocytes with ≥n foci. The integrated total body radiation dose was estimated from the dose volume histogram of patient's body corrected for the proportion of the body scanned by computed tomography for 3D treatment planning.Results: There was a strong linear correlation between the mean number of γ-H2AX foci per lymphocyte in the peripheral blood sample and integrated total body radiation dose (r = 0.83, p < 0.0001). The slope of the relationship was dependent on the site of body irradiated. In comparison to chest irradiation with a slope of 8.7 ± 0.8 foci Gy−1, the slopes for brain, upper leg and pelvic sites were significantly shallower by −4.7, −4.3, and −3.8 Gy−1, respectively (p < 0.0001), while the slope for upper abdomen irradiation was significantly larger by 9.1 ± 2.6 Gy−1 (p = 0.0007). There was a slight time effect since the start of radiotherapy on the slopes of the in vivo dose responses leading to shallower slopes (−1.5 ± 0.7 Gy−1, p = 0.03) later (≥10 day) during radiotherapy. After in vitro irradiation, lymphocytes showed 10.41 ± 0.12 foci per Gy with no evidence of inter-individual heterogeneity.Conclusions: γ-H2AX measurements in peripheral lymphocytes after local radiotherapy allow the estimation of the applied integral body dose. The site and time dependence have to be considered.

Adjuvant 5-FU-Based Chemoradiotherapy for Patients Undergoing R-1/R-2 Resections for Pancreatic Cancer

Background: Pancreatic cancer is the fifth leading cause of cancer-related death worldwide. Among patients treated with surgery alone, liver metastasis occurs in up to 50%, peritoneal recurrence in 25%, and local recurrence occurs in 50–80% of all patients who underwent resection. Even after a macroscopically curative resection, tumour cells might be observed by microscopy at one or more edges of the resected specimen in 20–51% (R-1) which might account for the high local recurrence. Aim of the Study: An analysis was performed in 54 patients who underwent an irradical resection (R-1 and R-2) for pancreatic cancer. 33 patients were treated with chemoradiotherapy. To evaluate the effect of therapy on survival and recurrence, this group was retrospectively compared to a group of 21 patients that did not receive chemoradiotherapy. Methods: Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses of 3 weeks, concomitant with intravenous 5-FU 25 mg/kg/24 h continuously on the first 4 days of each treatment course. Follow-up was performed mainly by CT scanning and occasionally by US and was completed for all but 1 patient. Results: The treatment protocol was completed in all patients without complications. Local recurrence was found in 6 (18%) patients in the group of patients who received adjuvant therapy versus 16 (48%) patients in the group that did not receive adjuvant therapy (p = 0.001). The median survival time for the treated group was 12.8 vs. 13.7 months in the group that did not receive chemoradiotherapy (p = 0.9). Three (9%) patients are still alive 140, 88 and 70 months after receiving surgery and adjuvant treatment. Conclusion: Adjuvant chemoradiotherapy clearly gives a significant better local control. However, treatment with 5-FU and radiotherapy does not improve survival due to distant metastases. This therapy probably prolongs survival in only a few patients. More effective treatment methods have to be designed to prevent metastatic disease and improve survival.

Treatment perspectives in locally advanced unresectable pancreatic cancer

Locally advanced unresectable pancreatic cancer is sometimes encountered without manifest distant metastases. Twenty patients with histologically proven unresectable pancreatic cancer without distant metastases were treated with radiotherapy and 5-fluorouracil (5-FU). Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses, concomitant with intravenous 5-FU 375 mg/m2 given as a bolus injection 4-6h before radiation on the first 4 days of each treatment course. The treatment protocol was completed in 18 patients without complications. The median survival time was 10 months which compares favourably with a 3-5 months median survival time when treatment is withheld. Nine patients (45 per cent) were alive at 1 year, two patients at 2, 3 and 4 years. A second-look operation was performed in four patients 6, 11, 12 and 22 months after completion of radiotherapy. In two patients the tumour could be resected. It appears that treatment with radiotherapy and 5-FU may benefit patients with locally advanced unresectable pancreatic cancer.

Locally Advanced Pancreatic Cancer Treated with Radiation and 5-Fluorouracil: A First Step to Neoadjuvant Treatment?

Aim of the Study: In two institutions, a retrospective analysis was performed on patients with histologically proven locally advanced pancreatic cancer without distant metastases. The aim of this analysis is to assess whether chemoradiotherapy provides survival benefit for patients with locally advanced pancreatic cancer. Methods: Forty-five patients from the Erasmus Medical Centre (Erasmus MC), Rotterdam, received 5-fluorouracil (5-FU) and radiotherapy and, 38 patients from the Academic Medical Centre Amsterdam (AMC) were offered the best supportive care. Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses, concomitant with intravenous 5-FU 25 mg/kg/ 24 h continuously on the first 4 days of each treatment course. Results: The treatment protocol was completed in 38 of 45 patients (84%) without complications. Radiological response was evaluated in 38 patients. Ten patients (26%) showed a partial response, stable disease was seen in 6 (16%) patients and progressive disease in 22 (58%) patients. A second-look operation was performed in 8 of 10 patients (72%) showing a radiological response, in 3 patients the tumour could be resected. Median overall survival time for the Erasmus MC group (n = 45) was 9.8 months compared to 7.6 months when the best supportive care was given (AMC group, p = 0.04). Conclusion: Although overall survival remains poor, treatment with 5-FU and radiotherapy might benefit some patients with locally advanced pancreatic cancer.

Outcome in surgically staged papillary serous and clear cell carcinoma of the uterus: A single institution experience

5108 Objective To determine the outcomes of surgically staged patients with I-IIIA uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CCC) of the uterus treated at Indiana University and compare their outcomes to patients treated on the Hoosier Oncology Group (HOG) 97–01 protocol involving intraperitoneal 32P and vaginal brachytherapy for a similar patient population. Methods Twenty-six patients with surgically staged FIGO stage I-IIIA UPSC or CCC were treated with standard, non-protocol adjuvant therapies at Indiana University Cancer Center between 1997 and 2003. Modality and distribution of therapies given to these patients included: no therapy (6), whole abdomen radiotherapy (WAR) (9), pelvic radiotherapy (4), intraperitoneal 32P with vaginal brachytherapy per HOG 97–01 protocol (3), and unsure (4). An additional 21 patients were treated on the Hoosier Oncology Group 97–01 protocol during the same time period. Patients treated on protocol received, in addition to complete surgical staging, 15 mCi of 32P administered intraperitoneally, followed by high dose-rate or low dose-rate vaginal cuff brachytherapy. Clinic charts, hospital records and pathology reports were reviewed for each patient. Results A total of 26 patients treated off HOG 97–01 protocol were reviewed and compared with the 21 patients who were treated on protocol. Patient characteristics and survival and recurrence data are listed in the following table. Conclusion In this population of limited-stage UPSC and CCC patients, recurrences in the abdomen and pelvis were much less common in the group treated with intraperitoneal 32P and vaginal brachytherapy. Therefore, further investigation using intraperitoneal radiocolloids combined with intracavitary brachytherapy in the adjuvant setting as an alternative to radiation therapy or chemotherapy is warranted in this group of patients after comprehensive surgical staging. No significant financial relationships to disclose.

915 poster Double-blind randomized clinical trial comparing prophilaxis vs. rescue treatment in patients (pts) undergoing fractionated upper abdomen radiotherapy (FUART)

915 poster Double-blind randomized clinical trial comparing prophilaxis vs. rescue treatment in patients (pts) undergoing fractionated upper abdomen radiotherapy (FUART)

Redução de dose e aumento na vida útil do tubo de raios X em tomografia computadorizada

OBJETIVO: Reduzir a dose de radiação e aumentar a vida útil do tubo de raios X em exames de tomografia computadorizada. MATERIAIS E MÉTODOS: Foram avaliados exames de crânio, abdome superior e tórax. Foi verificado se a técnica utilizada poderia ser alterada, foram sugeridos novos protocolos, e feitas comparações de qualidade da imagem, dose de radiação e aquecimento do tubo de raios X. RESULTADOS: Uma redução no mAs pôde ser feita sem comprometer a qualidade do diagnóstico, proporcionando redução de até 20% na dose média dos exames de crânio em adultos e de até 45% em crianças com idade de 0 a 6 meses; pacientes com menos de 50 kg tiveram redução de aproximadamente 37% na dose média de radiação para os exames de abdome superior; para o exame de tórax de rotina a redução chegou a 54%. O aquecimento do tubo de raios X para os exames de crânio, abdome superior e tórax teve redução estimada em aproximadamente 13%, 23% e 41%, respectivamente. CONCLUSÃO: Uma alteração nos protocolos dos exames descritos acarretará diminuição significativa na dose de radiação e aumento na vida útil do tubo de raios X, sem comprometer o diagnóstico.

Whole abdomen radiotherapy for patients with peritoneal dissemination of endometrial adenocarcinoma

Purpose No standard, universally accepted therapy exists for patients with adenocarcinoma of the endometrium with peritoneal dissemination. We report mature outcomes of selected patients with this uncommon pattern of spread treated with whole abdomen radiotherapy (RT). Methods and materials A retrospective review was undertaken of all patients with a diagnosis of endometrial cancer referred to the Radiologic Associates of Sacramento Medical Group between January 1, 1988 and October 1, 1999. Eleven patients were identified who had surgically proven peritoneal dissemination (peritoneal seeding) treated with whole abdomen RT as the sole cytotoxic therapy after operative cytoreduction. Ten patients had International Federation of Obstetrics and Gynecology (1988) Stage IV disease at diagnosis, and one had peritoneal dissemination at the time of initial recurrence after hysterectomy for Stage I disease. RT was administered to the whole abdomen using 10-MV photons in fractions of 1.0 or 1.5 Gy. A cumulative dose of 30 Gy was given in all patients, with shielding used to reduce the dose to the liver and kidneys. Partial abdominal volumes (pelvis plus paraaortic nodes) received supplementary dose at 1.5–1.8 Gy/fraction to bring the cumulative dose within the limited volumes to 46.2–54 Gy. Results Four patients developed progressive cancer within 13 months of completion of whole abdomen RT. One additional patient died of hepatic venoocclusive disease (radiation hepatitis) 15 months after RT without evidence of cancer recurrence. Five patients were alive and clinically cancer free 55, 129, 131, 134, and 178 months after RT completion. One patient died of unrelated causes 79 months after treatment completion. Conclusion Abdominal RT, in doses compatible with the acute and late tolerance of normal tissues, can eradicate small deposits of disseminated, intraperitoneal endometrial cancer. Currently, our patient selection criteria include limited peritoneal dissemination at diagnosis permitting complete surgical clearance (<1 mm residual) of visible and palpable disease, Grade 1 or 2 histologic features, lack of demonstrable extraabdominal metastasis, and absence of major medical contraindications.

Outcome and pattern of failure in pathological stage I-II papillary serous carcinoma of the endometrium: implications for adjuvant radiation therapy

Purpose/Objective: Papillary serous (PS) carcinoma of the endometrium is known to have a poor prognosis with a high rate of recurrence. Most patients present with advanced stage (FIGO stage III-IV) tumors and there is little information on outcome and optimal treatment of women with early stage disease. Patients with early stage disease are often grouped with advanced disease patients and treated with whole abdomen radiation therapy (WART) +/- chemotherapy in prior studies. Furthermore, most studies that have analyzed early stage disease have grouped PS with clear cell histology. As a result, the optimal management of these patients remains less defined. The purpose of this study is to evaluate the outcome and patterns of failure in women with pathological stage I-II PS carcinoma and discuss the implications for adjuvant radiation therapy (RT). Materials/Methods: Between 1990 and 2001, 868 endometrial carcinoma patients underwent primary surgery at our institution. Sixty-eight had papillary serous histologies, among which 23 (2.7%) had pathological stage I-II disease. All underwent TAH-BSO and assessment of peritoneal cytology. None received preoperative RT. Pelvic and para-aortic lymph node sampling were preformed in 12 and 8 patients, respectively. FIGO stages were: 3 IA, 8 IB, 6 IC, 5 IIA, and 1 IIB. The depth of myometrial invasion included: 3 none, 10 ≤1/2, and 10 >1/2. Cervical involvement was present in 6 patients. Adjuvant therapies included: 9 none, 10 RT (6 whole pelvic, 1 vaginal brachytherapy, 3 whole pelvic + vaginal brachytherapy), 4 chemotherapy (3 alone and 1 following whole pelvic RT), and 1 hormonal therapy alone. No patient received WART or para-aortic RT. Median follow-up was 38.7 months (range, 3-109 months). Results: The 5-year actuarial disease-free (DFS) and cause-specific (CSS) survivals for the entire group were 44% and 73.6%, respectively. Age, stage, and depth of myometrial invasion were not correlated with disease relapse. The overall failure rate was 35% (8/23). Five patients (22%) failed in the pelvis of which four relapsed in the vagina alone. There were no pelvic failures in patients treated with adjuvant RT. The 5-year actuarial pelvic recurrence rate was 27.5% and was 42.5% among the 13 women who did not receive RT compared with 0% among the 10 who did receive RT (p=0.06). Of note, patients treated with adjuvant RT had higher stage disease (p=0.02). Only 2 patients (8.7%) failed in the abdomen and both had a simultaneous distant recurrence. None had an isolated abdominal failure. The overall distant failure rate was 22% (5/23) and 4 of the failures occurred in patients who did not receive chemotherapy. Conclusions: Pathological stage I-II papillary serous carcinomas comprise a small percentage of patients with endometrial cancer. Although these women have organ-confined disease, recurrence is common particularly in the pelvis and distant sites. However, pelvic failure was effectively reduced by adjuvant pelvic RT. Unlike traditionally thought, abdominal recurrence was rare in our patients despite not delivering WART. The high rate of distant failure supports the use of chemotherapy. Our results suggest that the optimal approach to these patients is pelvic RT plus chemotherapy.

Feasibility and outcome of whole abdomen irradiation for patients with Non-Hodgkin’s lymphoma

Feasibility and outcome of whole abdomen irradiation for patients with Non-Hodgkin’s lymphoma

IMRT of large fields: whole abdomen irradiation

IMRT of large fields: whole abdomen irradiation

Radiation-induced emesis: a problem with many open questions.

Radiation-induced emesis (RIE) is often considered to be less frequent and less severe than nausea/vomiting encountered in patients receiving chemotherapy, although the issue has only been addressed in a few studies. It is possible that radiation oncologists undervalue the clinical relevance of RIE. If untreated, sickness produces an adverse effect on the patient's quality of life and may cause interruption of the treatment with possible unfavorable effects on tumor control. A prospective observational trial on RIE has recently been published by the Italian Group for Antiemetic Research in Radiotherapy (IGARR). The study evidenced that the overall cumulative incidence of vomiting and nausea occurred in about 40% of patients undergoing radiotherapy, and that the irradiated site, radiation field size, and previous chemotherapy were significant risk factors. Patients submitted to abdominal radiotherapy were at major risk of vomiting and nausea (71%), followed by those treated on the thorax, brain, head and neck, and pelvis (49%, 40%, 40%%, and 39%, respectively). Few small randomized clinical trials have evaluated the efficacy of various antiemetic drugs in preventing RIE. Generally, patients who entered these trials were those submitted to total body irradiation, half body irradiation or upper abdomen irradiation because of the greater risk of developing nausea and/or vomiting. The few controlled trials published have shown that dopamine receptor antagonists were effective in only about 50% of patients, whereas 5-hydroxytryptamine antagonists were more effective. Clinical practice guidelines for the use of antiemetics have recently been published by MASCC (Multinational Association of Supportive Care in Cancer) and ASCO (American Society of Clinical Oncology). Unfortunately, their recommendations were quite different, when classifying radiation emetogenic risk categories and when giving indications for the use of antiemetic drugs. However, MASCC and ASCO recommendations both suggested a prophylaxis with a 5-hydroxytryptamine antagonist and a corticosteroid for patients submitted to high emetogenic radiotherapy. There is evidence about the effectiveness of oral dexamethasone alone in fractionated upper abdomen radiotherapy and the use of a rescue antiemetic treatment as a possible alternative to the prophylaxis. Many questions remain open, and other prospective controlled trials on RIE are needed to answer them. Considering that radiotherapy to the abdomen, pelvis and thorax presents the most frequent problems in radiation oncology clinical practice, future trials on RIE should deal with these irradiated sites. The IGARR is carrying out a double-blind randomized clinical trial comparing prophylactic ondansetron plus dexamethasone versus ondansetron and dexamethasone given as a rescue treatment in patients undergoing fractionated radiotherapy to the upper abdomen.

Adjuvant radiochemotherapy in the treatment of completely resected, locally advanced gastric cancer

Purpose: To analyze the efficacy and toxicity of adjuvant whole abdomen irradiation (WAI) and concomitant chemotherapy in the treatment of completely resected, high-risk gastric cancer. Methods and Materials: Between October 1990 and September 1997, 52 patients with completely resected gastric cancer, with lymph node and/or serosal involvement, were treated. Ages were 16–78 (median, 53.5) years. Treatment was either total- or sub-total gastrectomy, followed by WAI, 2100 cGy/21 fractions plus a 2400 cGy/16 fractions boost to the tumor bed. Chemotherapy consisted of either 5-fluorouracil (5-FU) 450–500 mg/m 2 i.v. for 5 days first and 5th week or 200–300 mg/m 2 continuous infusion during irradiation. No further chemotherapy was given. Results: With a minimum follow-up of 30 months and a median follow-up of 43.5 months, 25 of the 52 patients have died. Overall 5-year survival rate is 54%. Three patients sustained Grade 3–5 complications. Two patients with Grade 5 complications (malabsorption syndrome) died 31 and 56 months after the beginning of the treatment, respectively, with no evidence of recurrent tumor. For patients with involvement of the lymph nodes alone ( n = 19) the 5-year survival was 69%, which was significantly better than the 36% 5-year survival observed for those patients with both serosal and lymph node involvement ( n = 26, p = 0.004). Conclusion: Adjuvant radiochemotherapy, WAI, and concomitant 5-FU, is a feasible and a fairly well-tolerated treatment for patients with locally advanced (involvement of the lymph nodes or serosa) gastric carcinoma who undergo complete resection. The 54% overall 5-year survival compares favorably with the survival reported after surgery alone for those patients.

Clear-cell and papillary serous cancer: treatment options

Clear-cell carcinoma (CCC) and serous papillary carcinoma of the endometrium (UPSC) are rare subtypes of endometrial carcinoma (10%). The histological diagnosis can be made on the dilation and curettage specimens in both types in a very high percentage of the cases. This is important in the planning of treatment. CCC and UPSC are associated with about 50% of all relapses occurring in endometrial carcinoma, and the 5-year survival rate is, on average, 42% and 27% respectively. Surgico-pathological stage, age, and vessel invasion are independent prognostic factors for both groups. The recurrence rate is extremely high, and the most frequent extra-pelvic sites of relapse are the upper abdomen, lungs and liver. Stage Ia patients treated with complete surgical staging alone have a low risk of relapse and need not be offered adjuvant systemic therapy or pelvic radiation. The treatment of patients with CCC and UPSC stage Ib, Ic, II and III should include radical debulking surgery and some form of adjuvant therapy, but it is not clear which type is most effective. Adjuvant pelvic radiotherapy plus intracavitary radiotherapy is usually given in early-stage disease and pelvic radio therapy/or whole abdomen irradiation plus adjuvant systemic chemotherapy (PAC) in advanced disease. However, we are urgently waiting for a large prospective randomized study to compare both modalities. Paclitaxel, alone or in combination, is currently being tested in phase II studies.

High-dose mitoxantrone + melphalan (MITO/L-PAM) as conditioning regimen supported by peripheral blood progenitor cell (PBPC) autograft in 113 lymphoma patients: high tolerability with reversible cardiotoxicity

Hematological and extrahematological toxicity of high-dose (hd) mitoxantrone (MITO) and melphalan (L-PAM) as conditioning regimen prior to peripheral blood progenitor cell (PBPC) autograft was evaluated in 113 lymphoma patients (87 at disease onset). Autograft was the final part of a hd-sequential (HDS) chemotherapy program, including a debulkying phase (1-2 APO +/- 2 DHAP courses) and then sequential administration of hd-cyclophosphamide, methotrexate (or Ara-C) and etoposide, at 10 to 30 day intervals. Autograft phase included: (1) hd-MITO, given at 60 mg/m2 on day -5; (2) hd-L-PAM, given at 180 mg/m2 on day -2; (3) PBPC autograft, with a median of 11 x 10(6) CD34+/kg, or 70 x 10(4) CFU-GM/kg, on day 0. A rapid hematological recovery was observed in most patients, with ANC >500/microL and Plt >20,000/microl values reached at a median of 11 and 10 days since autograft, respectively. The good hemopoietic reconstitution allowed the delivery of consolidation radiotherapy (RT) to bulky sites in 53 out of 57 candidate patients, within 1 to 3 months following autograft; five of these patients required back-up PBPC re-infusion due to severe post-RT pancytopenia. Few severe infectious complications were recorded. There was one single fatal event due to severe pancytopenia following whole abdomen RT. Cardiac toxicity was evaluated as left ventricular ejection fraction (LVEF), monitored by cardiac radionuclide scan. LVEF prior to and after autograft was significantly reduced (median values: 55% vs 46%) in 58 evaluated patients; however, a significant increase to a median value of 50% was observed in 45 patients evaluated at 1 to 3 years since autograft. At a median follow-up of 3.6 years, 92 patients are alive, with a 7-year overall survival projection and 6.7-year failure-free survival projection of 77% and 69%, respectively. We conclude that a conditioning regimen with hd-MITOIL-PAM fits well within the HDS program. It implies good tolerability and reversible cardiotoxicity and it may have contributed to the good long-term outcome observed in this series of patients.

Résultats d’un essai prospectif randomisé comparant une radiothérapie abdominopelvienne postopératoire et une chimiothérapie postopératoire dans les cancers de l’ovaire précoces

Purpose. – In a prospective randomized trial, our aim was to evaluate and compare the tolerance and efficacy of postoperative radiotherapy and chemotherapy in the treatment of early ovarian cancer. Material and methods. – Between 1990 and 1996, 150 patients with ovarian cancer stage IA, IB grades G2-3, and all patients classified IC and IIA, who did not have evidence of residual disease after surgery, were randomized to two treatment branches: radiotherapy or chemotherapy (CH). In the radiotherapy branch (76 patients), a whole abdomen irradiation of 30 Gy in 24 fractions over 5 weeks, with a pelvic boost to 50 Gy, was delivered. In the chemotherapy branch (74 patients) , there were six series of polychemotherapy separated with 3-weeks interval. In each series patients received association of cisplatin (50 mg/m 2, d1), adriamycin (50 mg/m 2, d1) and cyclophosphamide (500 mg/m 2, d1). Results. – The tolerance of the treatment was good and comparable in both groups. In the radiotherapy branch, three late grade G3 intestinal complications were observed (three bowel obstructions, which required surgery in two cases). The actuarial survival rate without evidence of disease was 81% at 5 years for both groups. In our series we found that histological grade had the strongest influence on survival prognosis; it was the only significant factor in a multivariate analysis. Patients with grade G3 tumors had the worst survival. Conclusion. – These data suggest that efficacy of postoperative radiotherapy and chemotherapy administered to our patients with early ovarian cancer gave approximately identical results.

Radiation-induced emesis: a prospective observational multicenter Italian trial

Purpose: A prospective observational multicenter trial was carried out to assess the incidence, pattern, and prognostic factors of radiation-induced emesis (RIE), and evaluate the use of antiemetic drugs in radiation oncology clinical practice.Methods and Materials: Fifty-one Italian radiation oncology centers took part in this trial. The accrual lasted 2 consecutive weeks, only patients starting radiotherapy in this period were enrolled. Exclusion criteria were age under 18 years, and concomitant chemotherapy. Evaluation was based on diary cards filled in daily by patients during radiotherapy and 1 week after stopping it. Diary cards recorded the intensity of nausea and any episode of vomiting and retching. Prophylactic and symptomatic antiemetic drug prescriptions were also registered.Results: Nine hundred thirty-four patients entered the trial, and 914 were evaluable. Irradiated sites were: breast in 211 patients, pelvis in 210 patients, head and neck in 136 patients, thorax in 129 patients, brain in 52 patients, upper abdomen in 42 patients, skin and/or extremities in 37 patients, and other sites in 97 patients. Vomiting and nausea occurred in 17.1% and 37.3% of patients, respectively, and 38.7% patients had both vomiting and nausea. At multifactorial analysis, the only patient-related risk factor that was statistically significant was represented by previous experience with cancer chemotherapy. Moreover, two radiotherapy (RT)-related factors were significant risk factors for RIE, the irradiated site and field size. In fact, a statistically significant higher percentage of RIE was registered in upper abdomen RT and RT fields > 400 cm2. Although nonstatistically significant, patients receiving RT to the thorax and head and neck presented a higher incidence of RIE. Only a minority (14%) of patients receiving RT were given an antiemetic drug, and the prescriptions were more often symptomatic than prophylactic (9% vs. 5%, respectively). Different compounds and a wide range of doses and schedules were used; however, there is some evidence from our data that in spite of antiemetic prophylaxis, 46% of patients had vomiting, and 58% had nausea. The majority (93%) of the prophylactic group received oral 5-hydroxytriptamine receptor (5-HT3) antagonist (8 mg/day, 7 days/week). In the symptomatic group, 54% and 41% patients received 5-HT3 antagonists and metoclopramide, respectively. At multivariate analysis, no patient- or RT-related risk factor for RIE was found to influence significantly the prophylactic or symptomatic use of antiemetics.Conclusion: Our study provided useful data on epidemiology and characteristics of RIE. Previous chemotherapy, field size, and irradiated site (upper abdomen) were the only significant prognostic factors of RIE. A remarkable incidence of RIE was found in patients submitted to thoracic and head and neck RT. With this background of knowledge, it will be possible to better plan further studies on this important problem. Moreover, the low rate of antiemetics use and the wide variety of doses and schedules employed suggest the need to reinforce the “evidence based” approach to identify the best antiemetic approach to RIE.

Sonographic detection of uterine and ovarian abnormalities in female survivors of Wilms' tumor treated with radiotherapy.

The purpose of this study was to use sonography to evaluate the size of the ovaries and uterus in survivors of Wilms' tumor who underwent radiotherapy. Eighteen survivors of Wilms' tumor had their ovaries and uterus measured on sonography. Their ages at diagnosis and treatment ranged from 14 months to 6 years. Four girls were prepubertal (age, 5-9 years), 11 were postpubertal (age, 11-30 years), and three had primary ovarian failure (age, 15-23 years) at the time of imaging. Findings were compared with those of a control group of 25 prepubertal and 25 postpubertal girls and women. Gonadotropin levels were measured. Three patients who underwent whole abdomen radiotherapy had elevated levels of gonadotropin and primary ovarian failure. Neither ovary was seen in two of the three patients and both ovaries were abnormally small (< or = 1 cm3) in the third patient. The uterus was abnormally small (length, < or = 4 cm) in all three of these patients even though two were being treated with hormone replacement therapy. Ten postpubertal patients who underwent hemiabdomen radiotherapy had normal gonadotropin levels and a normal-sized uterus on sonography; the ovary on the side that received radiotherapy was not seen in three of the 10 patients or was abnormally small (< or = 1.4 cm3) in two of the 10 patients compared with all normal ovaries in the postpubertal control group (p < .0001). One postpubertal patient with bilateral renal bed radiotherapy had normal ovaries and a normal-sized uterus. Significantly more patients in the postpubertal and ovarian failure radiotherapy group (5 [36%] of 14 patients) had one or both ovaries not seen than the control group (none [0%] of 25 patients; p = .0014). The uterus was significantly smaller than normal in three (23%) of the 13 patients in the postpubertal hemiabdomen and ovarian failure radiotherapy group versus none of the 25 patients in the postpubertal control group (p = .0339). Postpubertal female survivors of Wilm's tumor who underwent radiotherapy as children may have one or two small or absent ovaries and a small uterus that can be detected by sonography. The response of the uterus to hormone replacement therapy can also be assessed on sonography.