[Impact of chemotherapy on ovarian function and quality of life of patients with gestational trophoblastic neoplasia].

Objective: Using a questionnaire to evaluate different regimens of chemotherapy on ovarian function and quality of life of patients with gestational trophoblastic neoplasia (GTN) . Methods: At least 6 months after completion of chemotherapy, 200 patients with GTN treated in Peking Union Medical College Hospital from January 2010 to June 2017 were randomly selected to fill up the questionnaire. The questionnaire items were included the patient's menstrual cycles, sexual life, gestational issues and common health. The patients were divided into 3 groups by chemotherapy regimens: actinomycin D (Act-D) group, floxuridine+Act-D+vincristine (FAV) or floxuridine+Act-D+etoposide+vincristine (FAEV) group (FAV-FAEV group) , and etoposide+methotrexate+Act-D (EMA) /vincristine+cyclophosphamide (CO) or EMA/ etoposide+cisplatin (EP) group (EMA/CO-EMA/EP group) . Chi-square test was used with a significance level of P-value less than 0.05. Results: One hundred and seventy-three (86.5%,173/200) of the patients completed the questionnaire. Forty three point two percent (43.2%, 19/44) in the EMA/CO-EMA/EP group had a normal menstrual cycle, which were significantly lower than those of Act-D group (84.6%,22/26) and FAV-FAEV group (71.2%, 37/52; all P<0.05) . Amenorrhea rate was also significantly higher in EMA/CO-EMA/EP group (25.0%, 11/44) than in Act-D group (0) and FAV-FAEV group (17.3%, 9/52; all P<0.05) . The sexual life parameters were comparable among 3 groups. Ten out of thirty-two patients conceived after chemotherapy, 2 had miscarriages and 8 had full-term delivery of healthy babies. The common health and labor capacity were significantly decreased after chemotherapy (all P<0.05) . Conclusions: EMA/CO or EMA/EP regimen have a worse impact on ovarian function than Act-D and FAV or FAEV regimen. Gynecologic oncologist should be concerned about the ovarian function and quality of life of GTN patients.

Congenital-infantile fibrosarcoma of the foot--avoidance of amputation.

Congenital-infantile fibrosarcoma is a rare entity with a five year survival rate of over 90%. Surgery is still the most common treatment modality with amputation often necessary. There have been reports supporting the use of neoadjuvant chemotherapy to debulk the tumour in an effort to facilitate limb sparing surgery. We report a case of a newborn who presented with a life threatening haemorrhage from a fibrosarcoma of the foot, successfully treated with Vincristine, Actinomycin and Cyclophosphamide (VAC) chemotherapy alone.

Phase II study of vincristine, actinomycin-D, cyclophosphamide and irinotecan for patients with newly diagnosed low-risk subset B rhabdomyosarcoma: A study protocol.

BACKGROUND: Approximately 80% to 90% of patients with low-risk rhabdomyosarcoma can be cured. However, cured patients often face long-term complications associated with the treatment. An important factor in the treatment plan is the dose of cyclophosphamide administered because the dose can have both acute and long-term side effects. It is therefore essential to investigate whether the dose can be reduced without a negative effect on treatment outcome. The ARST0331 trial revealed that drastically reducing the cyclophosphamide dose to 4.8 g/m negatively affected treatment outcomes. The current study aims to determine whether reducing the cyclophosphamide dose to 10.8 g/m while introducing a new drug, irinotecan, can prevent the negative effect on treatment outcome. We also aim to investigate whether the reduced cyclophosphamide dose results in a decrease in infertility, one of the long-term complications of this treatment. METHODS: The subjects are patients with stage 1 group III rhabdomyosarcoma (excluding those with orbital group III N0 and NX) or patients with stage 3 group I and II low-risk subset B embryonal rhabdomyosarcoma who will alternately undergo VAC 1.2 treatment (vincristine, actinomycin D, cyclophosphamide 1.2 g/m) and VI treatment (vincristine, irinotecan). The effectiveness and safety of this treatment regimen will be assessed. Data will be presented at international conferences and will be published in peer-reviewed journals. DISCUSSION: This study is significant because it aims to establish that the use of irinotecan in patients with low-risk subset B embryonal rhabdomyosarcoma (aged 30 or younger) allows the dose of cyclophosphamide to be reduced and is associated with few short-term adverse effects and long-term complications. The open-label and single-arm design of this study may be a limitation. TRIAL REGISTRATION AND ETHICAL APPROVAL: The trial registration number is jRCTs051180200 (Japan Registry of Clinical Trials). The study protocol was approved by the institutional review board at each of the participating centers and the data will be presented at international conferences and published in peer-reviewed journals.

Methotrexate monotherapy for high-risk gestational trophoblastic neoplasia after therapy with etoposide, methotrexate, and dactinomycin: a case report.

We present a case of high-risk metastatic gestational trophoblastic neoplasia treated successfully with methotrexate monotherapy after severe toxicity from the combination chemotherapy: etoposide, dactinomycin, methotrexate, vincristine, and cyclophosphamide.

Renal failure does not preclude cure in children receiving chemotherapy for Wilms tumor: a report from the National Wilms Tumor Study Group.

BACKGROUND: Children with Wilms tumor can develop renal failure during treatment. Since there are few published data concerning the appropriate chemotherapy for this situation, we reviewed the experience of children who developed renal failure while being treated on National Wilms Tumor Study Group (NWTSG) studies 1-4 (1969-1994). PATIENTS AND METHODS: Data files in the NWTSG Data Center for all patients with Wilms tumor were screened. Patient demographics and tumor and treatment data were abstracted from those who developed renal failure. RESULTS: Twenty-eight of 5,910 (0.47%) children with Wilms tumor registered on NWTSG studies I through IV (1971-1994) were treated with chemotherapy after developing renal failure. Among these patients vincristine at full dose (0.05 mg/kg dose) did not increase the risk of severe toxicity. Dactinomycin (full dose: 15 mcg/kg day x 5) increased the risk for severe neutropenia when given at 75-100% of full dose. There was no compelling evidence for increased toxicity of doxorubicin when given at 100% versus 50% dosing (full dose: 20 mg/m(2) day x 3), but the number of patients analyzed was small. The overall survival percentage was 39%, but 64% for those patients who were in their initial treatment phase at the time of renal failure. CONCLUSION: The data suggest that, in the setting of renal failure, reduction of dosing is not necessary for the three main agents used for treatment of newly diagnosed Wilms tumor, and cure is not precluded. Accurate pharmacologic and pharmacokinetic studies are needed for any patient being treated while in renal failure.

[Preoperative adjuvant therapy for primary malignant bone tumors].

In primary bone sarcomas, the efficacy of chemotherapy varies according to the histological types. Prognoses are poor in patients with osteosarcoma or Ewing's sarcoma, when surgery alone is performed. However, because these sarcomas are chemosensitive, their prognoses have been improved with adjuvant chemotherapy. Nowadays, in highgrade bone sarcomas, especially in osteosarcoma, Ewing.s sarcoma and malignant fibrous histiocytoma of bone, adjuvant chemotherapy including neoadjuvant or preoperative chemotherapy is usually performed. The purpose of the neoadjuvant chemotherapy is (I) to prevent distant metastases, (II) to reduce the size of the primary tumor and (III) to evaluate the efficacy of the chemotherapeutic agents. Reducing the tumor size facilitates easier excision with less risk of local recurrence. In addition, not only limb-saving but also function-preserving surgery is made possible. Evaluating the efficacy of the chemotherapeutic agents in preoperative chemotherapy facilitates rational selection of postoperative chemotherapeutic agents. Several kinds of anticancer agents are used, and many authors have reported various kinds of protocols and their clinical results. Commonly used drugs include adriamycin, ifosfamide, cisplatin, methotrexate and vincristine in osteosarcoma, and vincristine, adriamycin, cyclophosphamide, ifosfamide, actinomycin-D and etoposide in Ewing's sarcoma. In contrast, chondrosarcomas are chemoresistant, and chemotherapy is rarely performed. Low-grade bone sarcomas, e. g., parosteal osteosarcoma, central low-grade osteosarcoma, are well cured only by surgical excision, and adjuvant chemotherapy is not performed for these low-grade sarcomas. To enhance the efficacy of preoperative chemotherapy, various modalities have been used e. g., intraarterial infusion, caffeine-assisted chemotherapy, and local perfusion with hyperthermia. Good clinical results have been reported.

Minimal invasive treatment of cervical rhabdomyosarcoma in an adolescent girl.

Rhabdomyosarcomas are the most common soft tissue sarcomas in childhood and adolescence. In cases of minimal cervical invasion, less invasive local excision in combination with adjuvant chemotherapy has resulted in excellent survival rates with complete preservation of the bladder, rectum, uterus and vagina. Herein we present the case of an adolescent girl with a large rhabdomyosarcoma of the uterine cervix treated with minimal invasive therapy.

FDG PET/CT demonstrates the effectiveness of isolated limb infusion for malignant melanoma.

A 43-year-old woman presented with a nodular melanoma treated with wide excision, split skin graft, and sentinel node biopsy. At 2-year follow up, she was noted to have clinical recurrence at the excision site. FDG PET/CT demonstrated in-transit metastasis in her left thigh in addition to disease at the site of the sentinel node biopsy. Isolated limb infusion was performed with melphalan and dactinomycin. PET/CT at 5 weeks demonstrated resolution of the in-transit metastasis and the disease at the excision site. This report of PET/CT demonstrates the effectiveness of chemotherapy for malignant melanoma delivered by isolated limb infusion.

[Etopside, methotrexate, kengshengmycin/etopside, cisplatin chemotherapy for chemorefractory gestational trophoblastic tumour].

OBJECTIVE: To evaluate the results of etopside, methotrexate, kengshengmycin/etopside, cisplatin (EMA/EP) chemotherapy in patients with chemorefractory gestational trophoblastic tumour. METHODS: Fifteen patients with chemorefractory gestational trophoblastic tumour were treated by EMA/EP chemotherapy schedule. RESULTS: Twelve of the fifteen cases were choriocarcinoma, and the other three were metastatic placental site trophoblastic tumour (PSTT). International Federation of Gynecology and Obstetrics (FIGO), 2 cases stage I, 10 cases stage III, 3 cases stage IV. Eight cases had FIGO score of 7 to 12, the score of the other 7 cases was over 12. Fifteen patients received a total of 93 cycles of the study regimen. The median number of courses for each patient was 6.2. Eleven cases (73%) achieved a complete remission while 3 patients (20%) had a partial remission, 1 case (7%) showed nonresponse. The main complications for EMA/EP chemotherapy were myelosuppression and gastrointestinal symptoms. CONCLUSIONS: The EMA/EP regimen is an effective treatment for chemorefractory gestational trophoblastic tumour, and the chemotherapeutic results can be further improved while combined with surgery and arterial infusion chemotherapy in the selected patients. Meanwhile, EMA/EP regimen should be considered in the primary management of patients with metastatic PSTT.

Treatment of non-metastatic rhabdomyosarcomas in childhood and adolescence. Results of the second study of the International Society of Paediatric Oncology: MMT84.

The second International Society of Paediatric Oncology (SIOP) study for rhabdomyosarcoma (MMT84) had several goals. The two principal aims were: (1) to improve the survival of children with rhabdomyosarcoma; and (2) to reduce the late effects from therapy by restricting the indications for surgery and/or radiotherapy after good response to initial chemotherapy. A further aim was to investigate the role of high-dose chemotherapy in young patients with parameningeal primary tumours. 186 previously untreated eligible patients entered the study. Patients with completely resected primary tumour received three courses of IVA (ifosfamide, vincristine and actinomycin D). Patients with incompletely resected tumour received six to 10 courses of IVA according to stage. Patients achieving complete remission with chemotherapy alone did not usually receive radiotherapy or undergo extensive surgery, but patients remaining in partial remission received local therapy with surgery and/or radiotherapy. Only patients over 5 years of age with parameningeal disease and patients over 12 years with tumours at any site were given systematic irradiation. Complete remission was achieved in 91% (170/186) of all patients. With a median follow-up of 8 years, the 5-year overall survival was 68% (+/- 3% standard error of the mean (SEM) and the 5-year event-free survival 53% (+/- 4% SEM). These results show an improvement over previous SIOP study (RMS75) in which survival was 52% and event-free survival was 47%. Among the 54 patients who exhibited isolated local relapse, 35% (19/54) survived in further remission longer than 2 years after retreatment, including local therapy (surgery +/- radiotherapy). Analysis of the overall burden of therapy received by all surviving children (including primary treatment and treatment for relapse if required) showed that 24% (28/116) were treated by limited surgery followed by three courses of IVA, 29% (34/116) were treated by chemotherapy alone (after initial biopsy) and 13% (15/116) received chemotherapy plus conservative local treatment (limited surgery or radiotherapy for residual disease). Only 34% (39/116) received intensive local therapy defined as radical wide field radiotherapy or radical surgery or both. Compared with the results obtained in the previous SIOP study, treatment in MMT84 was based on response to initial chemotherapy and, despite an overall reduction of the use of local therapy, significantly improved survival for patients with non-metastatic disease. This trial, also for the first time, provides evidence that retreatment after local relapse can achieve long-term second remissions.

Extraskeletal Ewing's sarcoma: a case report and review of the literature.

STUDY DESIGN: Case report. OBJECTIVES: To report on the diagnosis and current treatment of a rare tumor about the cervical spine. SUMMARY OF BACKGROUND DATA: Extraskeletal Ewing's sarcoma (EES) is rare and has not been previously described about the cervical spine. We present a case of a 24-year-old man with a large mass in the posterior triangle of the neck extending through the vertebral foramens of the cervical vertebrae. This was identified as an extraskeletal Ewing's sarcoma. Traditional treatment paradigms have been associated with a poor prognosis. Since the recommendations of the Intergroup Rhabdomyosarcoma Study II study of multimodal chemotherapy and radiotherapy, this tumor has a significantly better prognosis. METHOD: Surgical debulking of the tumor was necessary to relieve cord compression. Histologic analysis was used to confirm both magnetic resonance imaging and computed tomography diagnosis. A chemoradiation therapy program was commenced in accordance with Intergroup Rhabdomyosarcoma Study II recommendations. RESULTS: Computed tomography and magnetic resonance imaging demonstrated a large lobulated mass extending through the exit foramens of C2/C3 and C3/C4. The mass was entirely extraskeletal and extradural. Histologic examination of the excised mass showed microscopy consistent with extraskeletal Ewing's sarcoma. After surgical debulking and chemoradiation, the patient made a complete recovery. CONCLUSION: A review of the literature confirms that extraskeletal Ewing's sarcoma is a rare tumor and particularly so in the region of the cervical spine. Early diagnosis and surgical debulking combined with current multimodality chemoradiation programs can produce a favorable outcome.

EMA/EP chemotherapy for chemorefractory gestational trophoblastic tumor.

OBJECTIVE: To evaluate the results of etoposide/ methotrexate/actinomycin D/etoposide/cisplatin (EMA/ EP) chemotherapy in patients with chemorefractory gestational trophoblastic tumor (GTT). STUDY DESIGN: Fifteen patients with chemorefractory GTT were treated with EMA/EP. RESULTS: Twelve of the 15 cases were choriocarcinoma, and the last 3 were metastatic placental site trophoblastic tumor (PSTT): International Federation of Gynecology and Obstetrics (FIGO) stage I, 2 cases; stage III, 10 cases; stage IV, 3 cases. Seven cases have FIGO score 7-10; the scores of the remaining 8 cases were > 10. Fifteen patients received a total of 93 cycles of the study regimen. The median number of courses for each patient was 6.2. Eleven cases (73.3%) achieved complete remission, while 3 (20%) had partial remission; 1 case (6.7%) showed no response. The main complications of EMA/EP chemotherapy were myelosuppression and gastrointestinal symptoms. CONCLUSION: The EMA/EP regimen is effective for chemorefractory GTT, and the chemotherapeutic results can be improved when combined with surgery and arterial infusion chemotherapy in selected patients. The EMA/EP regimen should be considered for primary management of metastatic PSTT.

Safe, compact and portable system for regional chemotherapeutic hyperthermic perfusion procedures.

Perfusion techniques utilizing hyperthermic chemotherapy have been established as a successful modality of therapy for isolated metastatic malignant melanoma. The combination of chemotherapeutic agents (Dactinomycin, thiotepa and Mechlorethamine HCl) given in high doses, not possible systemically, combined with hyperthermia (40-42 degrees C) in an isolated extremity has shown greater tumor regression compared with systemic medication only. Many of the isolated limb perfusion procedures are performed in non-cardiac centers, especially at specialized cancer institutions. This often presents new obstacles for the perfusionist including lack of adequate perfusion equipment and disposables. Other obstacles include unfamiliarity of the operating room staff with the heart-lung machine and inappropriate and/or unsafe handling of the perfusion circuit. In order to overcome these obstacles and enhance safety, portability and effectiveness, the authors have developed an isolated limb perfusion system. The purpose of this study was to compare the parameters of treatment and long term outcomes demonstrated by our system and method, to previously published data. The qualitative comparative analysis was performed between eight treatments with this type of perfusion system and outcome data previously published. It is the authors' conclusion that the portable isolated limb perfusion system achieved all of the required parameters to provide safe and effective treatment for this type of melanoma. No demonstrated variation of the long term clinical results in our patient population was seen when compared to previously published data.

Isolated limb infusion with hyperthermia and chemotherapy for advanced limb malignancy: factors influencing toxicity.

BACKGROUND: The isolated limb infusion (ILI) technique is a simpler and less invasive alternative to isolated limb perfusion, which allows regional administration of high-dose chemotherapy to patients with advanced melanoma and other malignancies restricted to a limb. METHODS: Patients from two institutions, treated by ILI between 1998 and 2009 for extensive disease restricted to a limb, were included. The cohort included 31 patients with melanoma who presented with in-transit metastases or an extensive primary lesion, one patient with squamous cell carcinoma and another with epithelioid sarcoma not suitable for local surgical treatment. RESULTS: A complete response was achieved in 26.3% of patients and a partial response in 52.6%. Toxicity was assessed according to the Wieberdink limb toxicity scale. Grade II toxicity was noted in 39.5% of patients, grade III in 50% and grade IV in 10.5%. Toxicity was correlated with the results of a number of clinical and laboratory tests. The toxicity of melphalan and actinomycin D was dose-dependent. For melphalan, the relationship between toxicity and mean dose was as follows: grade II--34.7 mg; grades III and IV--47.5 mg (P = 0.012). The relationship between toxicity and maximum serum creatine phosphokinase (CPK) was as follows: grade II--431.5 U/L; grades III and IV--3228 U/L (P = 0.010). CONCLUSION: Toxicity after ILI is dose-dependent and serum CPK correlates with toxicity.

Comparison of pulsed actinomycin D versus 5-day methotrexate for the treatment of low-risk gestational trophoblastic disease.

OBJECTIVE: To determine the effectiveness of 2 standard chemotherapy regimens for low-risk gestational trophoblastic disease according to the International Federation of Gynecology and Obstetrics (FIGO) staging system. METHODS: From 2008 until 2010, 75 women with low-risk gestational trophoblastic disease received either pulsed actinomycin D (n=50) or 5-day methotrexate (n=25). The primary remission rate, the duration of treatment, the number of treatment courses, and the adverse effects were compared. RESULTS: The complete remission rates were 90% for the actinomycin D group and 68% for the methotrexate group (P=0.018). The mean number of chemotherapy courses administered to achieve complete remission (including courses of second-line therapy) was 3.1 in the methotrexate group and 5.3 in the actinomycin D group (P=0.01). No major adverse effects were experienced in either treatment group and there were no significant differences in terms of adverse effects. Second-line chemotherapy was indicated for 11 patients. CONCLUSION: Based on the present study, pulsed actinomycin D seems to be an appropriate first-line treatment for patients with low-risk gestational trophoblastic disease.

Use of an automated circuit for isolated limb infusion for malignancy.

BACKGROUND: Isolated limb infusion (ILI) for recurrent or in-transit melanoma is an accepted technique that allows high-dose chemotherapy to be delivered to an extremity with minimal systemic toxicity. Current infusion systems have relied on manual delivery of drugs and circulation of blood during the treatment. Herein, we document our initial results with an automated circuit for ILI as an alternative to the manual technique. METHODS: Patients undergoing ILI with an automated circuit for recurrent or advanced malignancy were identified. ILI was performed utilizing a Sarns 8000 roller pump attached to a Cobe 4:1 cardioplegia set with heat exchanger with a total priming volume of 80 ml. Melphalan (7.5 mg/L) and Dactinomycin (75 µg/L) doses which were corrected for ideal body weight were delivered via the infusion circuit after limb temperature reached 38 °C. RESULTS: Fourteen lower extremity infusion procedures were performed in 10 patients. Successful infusion procedures were completed in all patients using the automated circuit. Constant flow rates of 50-70 cc/minute were achievable with the automated circuit. Acute toxicity and clinical results were similar to that reported with manual delivery systems. CONCLUSION: ILI for advanced malignancy utilizing an automated circuit is feasible and safe. This automated system offers a safe and reliable alternative to the manual infusion technique.

Adult Wilms' tumor.

Adult Wilms' Tumor (AWT) is a rare entity arising from the metanephric blastema. There are only about 200 cases reported in world literature. The staging of AWT is done in the same way as in children according to the National Wilms' Tumour Stage Group (NWTSG). Definitive treatment plans for AWT are undefined but surgical treatment has the highest priority. There is also consensus on the need for multimodality approach. We report a case of AWT who remains disease free, three years after undergoing multimodality treatment.

Two consecutive phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the Children's Oncology Group.

PURPOSE: To estimate the antitumor activity and toxicity of irinotecan alone and in combination with vincristine when administered as window therapy and in combination with standard chemotherapy in pediatric patients with newly diagnosed metastatic rhabdomyosarcoma. PATIENTS AND METHODS: Nineteen patients younger than age 21 years with newly diagnosed metastatic rhabdomyosarcoma or undifferentiated sarcoma received window therapy with two cycles of irinotecan (20 mg/m2 daily for 5 days, repeated for 2 weeks) and 50 patients received window therapy with vincristine 1.5 mg/m2 (weeks 0, 1, 3, and 4) and two cycles of irinotecan (20 mg/m2 daily for 5 days, repeated for 2 weeks). Patients who achieved a partial response (PR) or complete response (CR) received these agents alternating with vincristine (V; 1.5/mg/m2), dactinomycin (A; 1.5 mg/m2), and cyclophosphamide (C; 2.2 g/m2) during weeks 6 through 41. Nonresponders were treated with VAC alone. Radiotherapy was administered to sites of disease at weeks 15 to 21. RESULTS: The window response rate (PR/CR) for patients who received irinotecan was 42% (95% CI, 38% to 80%) but the high progressive disease (PD) rate of 32% (95% CI, 11% to 52%) prompted closure of the trial. The window CR/PR rate for patients who received vincristine and irinotecan was 70% (95% CI, 57% to 83%), and the PD rate was only 8%. GI toxicities (abdominal pain, diarrhea, dehydration) were the most common adverse effects associated with the administration of irinotecan. CONCLUSION: The combination of vincristine and irinotecan is highly active in metastatic rhabdomyosarcoma. The different mechanism of action and nonoverlapping toxicity profile with VAC makes this combination an attractive candidate for further testing in intermediate risk patients with rhabdomyosarcoma.

Local recurrence and local control of non-metastatic osteosarcoma of the extremities: a 27-year experience in a single institution.

BACKGROUND: Indications and contraindications for limb salvage versus amputation for local treatment of osteosarcoma of the extremity are still controversial. PATIENTS AND METHODS: Patients (1,126) with non-metastatic osteosarcoma of the extremity, treated in a single institution between 1972 and 1999 with different protocols of adjuvant and neoadjuvant chemotherapy were evaluated to establish factors that could influence local recurrence (LR) and outcome. RESULTS: The 5-year event-free survival and overall survival were 55% and 66%. At a follow-up ranging between 5.5 and 32.5 years (mean18.6 years) of the 1,126 evaluated patients, 607 (54%) remained continuously disease-free and 519 relapsed. LR developed in 61 patients (5.4%) after a median time of 2.3 years (0.2-17). For this group of patients the 5-year post-relapse event-free survival and overall survival from the last relapse were, respectively, 11.4% and 16.4%. At the multivariate analyses only surgical margins and histologic response to preoperative treatment resulted to be independent prognostic factors for LR. CONCLUSION: Considering the risk of LR after surgery with inadequate surgical margins and poor prognosis of LR in osteosarcoma, limb salvage procedures should be performed only when adequate margins surgical margins can be achieved. In case of inadequate margins, an immediate amputation should be considered.