The aim of this prospective study conducted in three French comprehensive cancer centers was to evaluate the therapeutic impact on survival of laparoscopic para-aortic (PA) staging surgery in locally ...advanced cervical cancer (LACC) before chemoradiotherapy.
We conducted a prospective multicenter study of 237 patients treated from 2004 to 2011 for LACC with negative positron emission tomography (PET) imaging of the PA area and undergoing laparoscopic PA lymphadenectomy. Radiation fields were extended to the PA area when PA nodes were involved. Chemoradiotherapy modalities were homogeneous across institutions. Patients with a poor prognosis histologic subtype or peritoneal carcinosis were excluded.
Patients had clinical International Federation of Gynecology and Obstetrics stages IB2 (n = 79), IIA (n = 10), IIB (n = 121), III (n = 22), or IVA (n = 5). One hundred ninety-nine patients had squamous carcinoma, and 38 had adenocarcinoma/adenosquamous lesions. Twenty-nine patients (12%) had nodal involvement (false-negative PET-computed tomography CT results)-16 with a PA nodal metastasis measuring more than 5 mm and 13 with a nodal metastasis measuring ≤ 5 mm. Event-free survival rates at 3 years in patients without PA involvement or with PA metastasis measuring ≤ or more than 5 mm were 74% (SE, 4%), 69% (SE, 21%), and 17% (SE, 14%; P < .001).
To our knowledge, this is the largest series of patients reported undergoing such a strategy. We obtained the same survival rate for patients with PA nodal metastasis ≤ 5 mm and patients without PA lymph node involvement, suggesting that this strategy is highly efficient in such patients. Conversely, the survival of patients with PA nodal involvement greater than 5 mm remained poor, despite the absence of extrapelvic disease on PET-CT imaging in this subgroup.
To identify risk factors associated with outcome in children with metastatic rhabdomyosarcoma in a large cohort of patients
Pooled data were obtained from 788 patients treated in nine studies ...performed by European and American cooperative groups. Clinical factors, including age, histology, site of primary, and site(s) and number of sites of metastatic disease, were correlated with event-free survival (EFS) and overall survival (OS).
Seven hundred eighty-eight patients were eligible for analysis. The 3-year OS and EFS were 34% (SE, 1.7) and 27% (SE, 1.6), respectively. By univariate analysis, 3-year EFS was significantly and adversely influenced by age, alveolar histology, location of primary tumor in unfavorable site (defined as extremity and "other" sites), presence of three or more sites of metastatic disease, and the presence of bone or bone marrow involvement. By multivariate analysis, EFS was strongly correlated to all factors except histology. Relative risks were 1.6 for age younger than 1 year or at least 10 years, 1.4 for unfavorable site of primary tumor, 1.4 for bone or bone marrow involvement, 1.4 for three or more metastatic sites. EFS was 50% for patients without any of these four adverse factors and was respectively 42%, 18%, 12%, and 5% in patients with one, two, three, or four factors (P < .0001).
This analysis identified subsets of patients with metastatic rhabdomyosarcoma with different outcomes to current therapy and offers a strategy to define patient candidates for experimental approaches to treatment.
To retrospectively analyze the clinical features and results of treatment in 56 infants with fibrosarcoma enrolled onto cooperative European protocols between 1979 and 2005 and treated with a ...combination of surgery and chemotherapy.
We performed a retrospective case review of infants under the age of 2 years with fibrosarcoma treated between 1979 and 2005 in six European studies. Patients were staged according to the Intergroup Rhabdomyosarcoma Staging System international classification as a function of the type of initial surgery and the extent of disease and were treated with surgery and chemotherapy. Survival was calculated using the Kaplan-Meier method.
Primary tumor site was the limbs in 66% of patients; median tumor diameter was more than 5 cm in 63% of patients; and postoperative staging was as follows: group I, 22%; group II, 27%; group III, 47%; and group IV, 4%. Response rate to chemotherapy was 75%, and the specific response rate to vincristine-dactinomycin was 71%. Local control was obtained in 84% of patients. At the end of follow-up, 45% of survivors had been treated by surgery alone, 6% by chemotherapy alone, 46% by surgery and chemotherapy, and 2% by surgery, chemotherapy, and radiotherapy. The 5-year overall survival (OS) rate was 89%. The 5-year OS and event-free survival rates for localized patients were 89% and 81%, respectively.
Although complete resection is rarely feasible at diagnosis, conservative surgery remains the mainstay treatment for infantile fibrosarcoma. An alkylating agent-free and anthracycline-free regimen is usually effective and should be chosen as first-line chemotherapy for inoperable tumors. Overall prognosis is good, but progression or relapse, mainly local, remains possible.
Ifosfamide is widely used in pediatric oncology but its nephrotoxicity may become a significant issue in survivors. This study is aimed at evaluating the incidence of late renal toxicity of ...ifosfamide and its risk factors.
Of the 183 patients prospectively investigated for renal function, 77 treated for rhabdomyosarcoma, 39 for other soft tissue sarcoma, 39 for Ewing's sarcoma, and 28 for osteosarcoma were investigated at least 5 years after treatment. No patients had received cisplatin and/or carboplatin. Glomerular and tubular functions were graded according to the Skinner system.
The median dose of ifosfamide was 54 g/m(2) (range, 18 to 117 g/m(2)). After a median follow-up of 10 years, 89.5% of patients had normal tubular function, and 78.5% had normal glomerular function rate (GFR). Serum bicarbonate and calcium were normal in all patients. Hypomagnesemia was observed in 1.2% and hypophosphatemia in 1%. The tubular threshold for phosphate was reduced in 24% of the patients (grade 1 in 15%, grade 2 in 8%, and grade 3 in 0.5%). Glycosuria was detected in 37% of the patients but was more than 0.5 g/24 hours in only 5%. Proteinuria was observed in 12%. Ifosfamide dose and interval from therapy to investigations were predictors of tubulopathy in univariate and multivariate analysis. In a multivariate analysis, an older age at diagnosis and the length of interval since treatment had independent impacts on the risk of abnormal GFR.
Renal toxicity is moderate with a moderate dose of ifosfamide. However, since it can be permanent and can get worse with time, repeated long-term evaluations are important, and this risk should be balanced against efficacy.
Previous studies suggest poor outcome in children with relapsed rhabdomyosarcoma (RMS). A better understanding is needed of which patients can be salvaged after first relapse.
The analysis included ...children with nonmetastatic RMS and embryonal sarcoma enrolled onto the International Society of Paediatric Oncology (SIOP) Malignant Mesenchymal Tumor (MMT) 84, 89, and 95 studies who relapsed after achieving complete local control with primary therapy. All patients included in the analysis had follow-up for ≥ 3.0 years after the last event. The clinical features, initial treatment characteristics, and features of the relapse were correlated with survival in univariate and multivariate analyses.
In all, 474 eligible patients were identified for the study. At ≥ 3.0 years from the last event, 176 (37%) were alive ("cured"). In a full-model multivariate analysis, the factors identified at first relapse that most strongly associated with poor outcome were metastatic relapse (odds ratio OR, 4.19; 95% CI, 2.0 to 8.5), prior radiotherapy treatment (OR, 3.64; 95% CI, 2.1 to 6.4), initial tumor size > 5 cm (OR, 2.53; 95% CI, 1.5 to 4.1), and time of relapse < 18 months from diagnosis (OR, 2.20; 95% CI, 1.3 to 3.6). Unfavorable primary disease site, nodal involvement at diagnosis, alveolar histology, and previous three- or six-drug chemotherapy were also independently associated with poor outcome. To estimate chance of cure for individual patients, a nomogram was developed, which allowed for weighting of these significant factors.
Some children with relapsed RMS remain curable. It is now possible to estimate the chance of salvage for individual children to direct therapy appropriately toward cure, use of experimental therapies, and/or palliation.
To improve outcome for children with nonmetastatic rhabdomyosarcoma and to reduce systematic use of local therapy.
Five hundred three previously untreated patients aged from birth to 18 years, ...recruited between 1989 and 1995, were allocated to one of six treatment schedules by site and stage.
Five-year overall survival (OS) and event-free survival (EFS) were 71% and 57%, respectively. Primary site, T-stage, and pathologic subtype were independent factors in predicting OS by multivariate analysis. Differences between EFS and OS reflected local treatment strategy and successful re-treatment for some patients after relapse. Patients with genitourinary nonbladder prostate tumors had the most favorable outcome (5-year OS, 94%): the majority were boys with paratesticular tumors treated successfully without alkylating agents. Patients with stage III disease treated with a novel six-drug combination showed improved survival compared with the Malignant Mesenchymal Tumor 84 study (MMT 84; 5-year OS, 60% v 42%, respectively). OS was not significantly better than that achieved in the previous MMT 84 study, but 49% of survivors were cured without significant local therapy.
Selective avoidance of local therapy is justified in some patients, though further work is required to prospectively identify those for whom this is most applicable. Exclusion of alkylating agents is justified for the most favorable subset of patients. The value of the new six-drug chemotherapy combination is being evaluated further in a randomized study (MMT 95).
Learning Objectives
After completing this course, the reader will be able to:
Rate the prognostic factors for overall survival in patients undergoing completion surgery after initial chemoradiation ...therapy (CRT) for locally advanced cervical cancer.
In cervical cancer patients undergoing completion surgery, consider using laparoscopy to decrease the morbidity of the surgery.
In cervical cancer patients undergoing completion surgery, use PET‐CT imaging to improve detection of para‐aortic involvement.
This article is available for continuing medical education credit at CME.TheOncologist.com
Purpose.
The aim of this study was to evaluate the prognostic factors and morbidities of patients undergoing completion surgery for locally advanced‐stage cervical cancer after initial chemoradiation therapy (CRT).
Patients and Methods.
Patients fulfilling the following inclusion criteria were studied: stage IB2–IVA cervical carcinoma, tumor initially confined to the pelvic cavity on conventional imaging, pelvic external radiation therapy with delivery of 45 Gy to the pelvic cavity and concomitant chemotherapy (cisplatin, 40 mg/m2 per week) followed by uterovaginal brachytherapy, and completion surgery after the end of radiation therapy including at least a hysterectomy.
Results.
One‐hundred fifty patients treated in 1998–2007 fulfilled the inclusion criteria. Prognostic factors for overall survival in the multivariate analysis were the presence and level of nodal spread (positive pelvic nodes alone: hazard ratio HR, 2.03; positive para‐aortic nodes: HR, 5.46; p < .001) and the presence and size of residual disease (RD) in the cervix (p = .02). Thirty‐seven (25%) patients had 55 postoperative complications. The risk for complications was higher with a radical hysterectomy (p = .04) and the presence of cervical RD (p = .01).
Conclusion.
In this series, the presence and size of RD and histologic nodal involvement were the strongest prognostic factors. Such results suggest that the survival of patients treated using CRT for locally advanced cervical cancer could potentially be enhanced by improving the rate of complete response in the irradiated area (cervix or pelvic nodes) and by initially detecting patients with para‐aortic spread so that treatment could be adapted in such patients. The morbidity of completion surgery is high in this context.
The study evaluates the prognostic factors and morbidities of patients undergoing completion surgery for locally advanced‐stage cervical cancer after initial chemoradiation therapy.
The purpose of this study was to determine patient characteristics and outcomes for bladder/prostate (BP) rhabdomyosarcoma (RMS) using an international cohort of prospectively treated patients ...comparing different treatment algorithms. Data were collected from 379 patients (1979–1998) treated on protocol; Intergroup Rhabdomyosarcoma Study, IRS‐IV (n = 239 patients), International Society of Pediatric Oncology Malignant Mesenchymal Tumors (MMT) Committee MMT‐84 and ‐89 (n = 74), Italian Cooperative Group, RMS‐79 and RMS‐88 Studies (n = 37) or German Cooperative Soft Tissue Sarcoma Study CWS‐91 protocols (n = 29). A total of 322 (85%) patients had localized embryonal RMS (ERMS) and 27 had metastatic disease. Thirty patients (21 local disease; 9 metastatic) had nonembryonal BP RMS. Patients with localized ERMS had large tumors (64% >5 cm) that were invasive (54%) with uninvolved regional lymph nodes (N0, 93%). The 5‐year failure‐free survival (FFS) was 75% and the overall survival (OS) was 84%, with 89% of deaths attributed to disease. Treatment failures were usually local disease recurrence (60%). Predictors of FFS included T‐stage (invasiveness), size, and histology. FFS was decreased for patients not receiving initial radiotherapy but this did not translate into a decreased OS. The 21 patients with localized nonembryonal BP RMS had a FFS and OS of 47%. The 36 patients with metastatic disease were more likely to be older and had large tumors that were invasive with alveolar histology and regional lymph node involvement. The 5‐year FFS and OS were 41 and 44%, respectively. In conclusion, the majority of BP RMS patients had localized ERMS with a resultant good prognosis using current treatment algorithms. There were differences in FFS between treatment protocols but this did not result in an altered OS.
Histologic results of complete para-aortic lymphadenectomy were studied in patients treated for stage IB2/II cervical carcinoma who had no para-aortic uptake on (18)Ffluorodeoxyglucose positron ...emission tomography combined with integrated computed tomography (FDG-PET/CT).
Patients were treated between 2004 and 2006 for stage IB2/II cervical cancer. Magnetic resonance imaging of the abdomen and pelvis and FDG-PET/CT were initially performed. Patients with no para-aortic abnormalities were treated with external pelvic radiation therapy and concomitant chemotherapy followed by utero-vaginal brachytherapy. Para-aortic lymphadenectomy was then performed. FDG-PET/CT images were reviewed by two nuclear medicine specialists.
Thirty-eight patients were studied. Three patients had histologically proven para-aortic involvement (metastatic nodes with capsular rupture in the para-aortic area), leading to a negative predictive value of 92% for para-aortic nodal involvement.
In this study, three of 38 patients with no para-aortic uptake on (18)FFDG-PET/CT imaging had histologically proven para-aortic node involvement. PET/CT imaging without histologic examination of the para-aortic area used to determine radiation therapy fields in stage IB2/II cervical cancer would overlook 8% of patients with histologic para-aortic nodal involvement.
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