Cyclophosphamide, Doxorubicin, Vincristine Research Articles

Angiosarcoma in children: the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and literature review

Angiosarcoma is a rare and highly malignant endothelial tumor, which occurs mainly in adults and is extremely rare in children and adolescents. The German guidelines for the treatment of soft tissue sarcomas provided by the Cooperative Weichteilsarkom Studiengruppe in 2012 included a separate therapeutic regimen for pediatric angiosarcoma consisting of a combination of vincristine/doxorubicin/cyclophosphamide (VDC) and paclitaxel. The aim of this article was to describe the epidemiological, clinical, and morphological characteristics of angiosarcoma, to review treatment approaches, and to present the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation in the treatment of children with angiosarcoma. Our study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. The study included 5 patients diagnosed with angiosarcoma who had received treatment between 2012 and 2022. The patients’ parents gave consent to the use of their child's data, including photographs, for research purposes and in publications. Data on the patients’ age, gender, tumor location and extension, performed treatment and outcomes of the disease were analyzed. The male:female ratio was 0.66:1 and the median age was 5.2 years. Tumors were located in the soft tissues (n = 3) and in the bones (n = 2). In all the cases, invasion of the surrounding tissues was observed. There were no distant metastases at the time of diagnosis. Two (40%) patients underwent primary resection (R1) and 3 (60%) patients had tumor biopsy. Four patients received therapy according to the German guidelines for the treatment of angiosarcoma (VDC/paclitaxel courses), and 1 patient received treatment according to the guidelines for the management of non-rhabdomyosarcoma soft-tissue sarcomas (courses with vincristine, ifosfamide, doxorubicin/ vincristine, ifosfamide, actinomycin D). Objective response to treatment was achieved in 3 (60%) cases. Local control treatment of these 3 patients consisted of radiation therapy with a total dose of 50.4 Gy after R1 resection in 2 cases and biopsy in 1 case. After a median follow-up of 32 months, 2 patients who had received VDC/paclitaxel were alive without events (with complete and partial response), 3 patients died of progressive disease. Our data confirm the aggressive behavior of angiosarcoma in children. Protocol therapy that includes multiagent chemotherapy based on paclitaxel and doxorubicin along with local control treatment makes it possible to achieve a long-term control of the disease in some patients. However, further research on molecular and genetic characteristics of angiosarcoma is required to find potential novel targets for molecular targeted therapy. Further studies investigating the effectiveness of checkpoint inhibitors in angiosarcoma are also needed.

153P Safety profile and associated costs of therapies for relapsed small cell lung cancer in Switzerland

Small cell lung cancer (SCLC) is an aggressive disease with poor prognosis, in particular in the relapsed setting. Treatments for relapsed SCLC remain limited with no new recent approvals in Europe. Lurbinectedin was granted FDA accelerated approval for patients with SCLC with disease progression after platinum containing therapy. Differences exist with respect to adverse events (AE) among therapies for 2LSCLC. Our aim was to compare the cost of managing adverse events in 2L treatment of SCLC with recommended therapies and with lurbinectedin in Switzerland. The relevance of guideline-adherent comparators in routine clinical practice was verified by Swiss clinical expert opinion. AE ≥ grade 3 related to treatment were derived from RCTs of 2L SCLC with topotecan (oral and IV), CAV (cyclophosphamide + doxorubicin + vincristine), etoposide + carboplatin and from the phase II B-005 trial of lurbinectedin monotherapy in 2LSCLC. Resource use and unit costs were obtained from published literature, national tariffs and clinical expert opinion. Scenario analysis with upper and lower limits of incidence of AEs and costs associated with each AE were constructed. Base case results for costs of AE management were CHF 9,238 (€8,421) per patient per treatment course (typically 4 cycles) for oral topotecan, CHF 8,608 (€7,847) for IV topotecan; CHF 5,155 (€4,699) for etoposide plus carboplatin, CHF 4,942 (€ 4,505) for CAV and CHF 1,346 (€1,227) for lurbinectedin. Scenario analyses: lower limit (LL) CHF 1,067 (€973) for lurbinectedin, CHF 2,716 (€2,476)-CHF 5,582 (€5,088) for standard treatments. Upper limit (UL) CHF 1,625 (€1,481) for lurbinectedin, CHF 5,853 (€5,335)-CHF 12,895 (€11,755) for standard treatments. The most frequently used treatments for 2L SCLC in Switzerland are carboplatin + etoposide and CAV, followed by IV topotecan. On average, lurbinectedin was associated with cost savings of 81% (74%-85%) compared to standard treatments. A subanalysis limited to recent trials (published 2020-2021) showed reproducibility of results. Lurbinectedin is associated with substantially lower cost for AE treatment compared to existing 2L SCLC treatments in Switzerland.

Extracranial rhabdoid tumours: Results of a SFCE series of patients treated with a dose compression strategy according to European Paediatric Soft tissue sarcoma Study Group recommendations

Background and aimsExtracranial malignant rhabdoid tumours are tumours that mainly affect young children and have a poor prognosis. In 2014, the European Paediatric Soft-tissue sarcoma Study Group developed treatment recommendations consisting in intensive dose chemotherapy every 2 weeks using vincristine-doxorubicin-cyclophosphamide (VDCy) and ifosfamide-etoposide (IE) associated with early surgery and irradiation of tumour sites. MethodsA retrospective study was conducted on children treated in France by these new recommendations up to January 2019. ResultsThirty-five patients were identified. The primary tumour was in miscellaneous soft parts for 18 patients, in the kidney for 11 and in the liver for six. The median age at diagnosis was 17.5 months (range 1.2–198.2). Distant locations (metastatic or synchronous tumours) were present in 37.1% at diagnosis. SMARCB1 germline pathogenic variant was detected in 17.1% of patients. Overall tolerance was good, with 87–97% of theoretical chemotherapy cumulative doses actually delivered. The median interval between two courses was 18 days. Surgical resection was performed in 83% (19 R0, 7 R1 and 3 R2) and local radiotherapy in 49% of patients. After a median follow-up of 50.4 months (range 16.5–134.1), the 2-year overall and event-free survivals were 47.6% (95% confidence interval [CI] 30.2–63.1) and 42.9% (95% [CI] 26.5–58.3), respectively. On univariate analyses, localised disease and gross total resection were significantly associated with favourable outcomes. ConclusionsIntensive dose chemotherapy with VDCy/IE can be administrated with no remarkable short-term toxicity, including in infants. However, the outcome remains poor for patients without gross total resection and with metastatic or multifocal disease. These patients could be stratified into a high-risk group that requires a new immediate therapeutic approach such as targeted agents combined with multimodal therapy.

Local Lung Mass Masquerading a Very Aggressive Extraskeletal Ewing Sarcoma Presenting as Bilateral Paraparesis in a Young Adult

Ewing sarcoma is typically seen in children involving long bones. Although well described, its presentation in extraskeletal tissues is relatively rare and is classified as an Ewing sarcoma family of tumors. They are mostly curable when they occur in children. An extraskeletal Ewing sarcoma in adults is uncommon, limiting the experience in adult oncologists. The biopsy is essential for definitive diagnosis, which shows small round blue cells that must be differentiated from lymphoma, embryonal rhabdomyosarcoma, and small cell carcinoma. Management is multimodal, involving surgery, radiation for local treatment of primary tumor, and systemic chemotherapy. A multidisciplinary approach, coupled with risk-adapted intensive neoadjuvant and adjuvant multi-agent chemotherapies and other modalities such as radiation and surgery for control of the primary site and metastatic disease, is needed. The primary multidrug chemotherapy regimen consists of alternating cycles of vincristine/doxorubicin/cyclophosphamide (VDC) and ifosfamide/etoposide (IE) given every 2 weeks with growth factor support. Prognosis and the 5-year survival rate are better for localized than the metastatic disease, and in metastatic disease, it is better for patients with lung metastasis than other metastatic disease sites. We describe a rare extraskeletal tumor arising from a lung that tested positive for Ewing sarcoma, also known as Askin’s tumor in a young adult. In our case, the tumor rapidly metastasized locally to involve the thoracic spine causing paraparesis. Timely diagnosis and early management are essential to improve outcomes. We also present how treatment can be delayed due to sepsis and emphasize the careful multispecialty approach’s importance. J Med Cases. 2020;11(12):388-393 doi: https://doi.org/10.14740/jmc3582

Local Lung Mass Masquerading a Very Aggressive Extraskeletal Ewing Sarcoma Presenting as Bilateral Paraparesis in a Young Adult

Ewing sarcoma is typically seen in children involving long bones. Although well described, its presentation in extraskeletal tissues is relatively rare and is classified as an Ewing sarcoma family of tumors. They are mostly curable when they occur in children. An extraskeletal Ewing sarcoma in adults is uncommon, limiting the experience in adult oncologists. The biopsy is essential for definitive diagnosis, which shows small round blue cells that must be differentiated from lymphoma, embryonal rhabdomyosarcoma, and small cell carcinoma. Management is multimodal, involving surgery, radiation for local treatment of primary tumor, and systemic chemotherapy. A multidisciplinary approach, coupled with risk-adapted intensive neoadjuvant and adjuvant multi-agent chemotherapies and other modalities such as radiation and surgery for control of the primary site and metastatic disease, is needed. The primary multidrug chemotherapy regimen consists of alternating cycles of vincristine/doxorubicin/cyclophosphamide (VDC) and ifosfamide/etoposide (IE) given every 2 weeks with growth factor support. Prognosis and the 5-year survival rate are better for localized than the metastatic disease, and in metastatic disease, it is better for patients with lung metastasis than other metastatic disease sites. We describe a rare extraskeletal tumor arising from a lung that tested positive for Ewing sarcoma, also known as Askin’s tumor in a young adult. In our case, the tumor rapidly metastasized locally to involve the thoracic spine causing paraparesis. Timely diagnosis and early management are essential to improve outcomes. We also present how treatment can be delayed due to sepsis and emphasize the careful multispecialty approach’s importance.

3 cases of undifferentiated embryonal sarcoma of the liver (UESL) in adult

Abstract Background UESL is a malignant mesenchymal tumor mainly occurring in children between the ages of 5-10 years, and rare in adult. There is no established treatment for UESL, so it is treated with agent commonly used for pediatric sarcoma. Here, we report 3 cases of UESL in our department from 2008 to 2018. Case 1 The patient was a 30-year-old female. She noticed upper abdominal pain, and a tumor was found in the left upper abdomen. She underwent complete resection and did not receive adjuvant chemotherapy (AC). 9 months later, she had a first recurrence. She received ifosfamide (IFM) monotherapy followed tumor resection. However, she had recurrence again and was subsequently treated with monotherapy of eribulin, trabectedin, and dacarbazine, she died of drug-induced lung injury due to dacarbazine after 3 years and 9 months from diagnosis. Case 2 The patient was a 18-year-old female. She had a epigastric pain and intra-hepatic hemorrhage due to liver tumor was found. The tumor was completely resected at elective surgery following emergency hemostatic therapy. 3 months later, she had recurrence and received doxorubicin (DXR) + IFM therapy followed residual tumor resection. She is alive without recurrence over 2 years after surgery. Case 3 The patient was a 20-year-old female. She noticed epigastric pain and she was treated as a liver abscess. Next month, perforation of the right hepatic lobular mass was found. She had trisegmentectomy, but complete resection was difficult due to infiltration to other organs. We considered that the remaining lesion will increase in high probability, we have started VDC (Vincristine, DXR, Cyclophosphamide) therapy and now on going. Conclusion Two cases who did not received AC had recurrence in a short period after surgery despite complete resection, and one is currently continuing AC. These show that USEL in adult is at high risk of recurrence. Further study is needed to develop therapy for embryonal sarcoma especially in adult.

The addition of cycles of irinotecan/temozolomide (i/T) to cycles of vincristine, doxorubicin, cyclophosphamide (VDC) and cycles of ifosfamide, etoposide (IE) for the treatment of Ewing sarcoma (ES).

10533Background: Treatment for ES in North America has evolved to include cycles of VDC and IE. A regimen including these 5 agents with interval dose compression has achieved 5 year EFS of 73% for ...

Rhabdomyosarcoma (RMS) in adults: Histologic subtypes and overall survival with actinomycin-based chemotherapy vs doxorubicin-based chemotherapy.

11073 Background: RMS typically occurs in children. Vincristine, Actinomycin and Cyclophosphamide (VAC) based chemotherapy is the current standard. Limited data exist on the frequency of the histologic subtypes and optimal chemotherapy regimen for the treatment of adult patients with RMS. Methods: We retrospectively identified patients ≥18 years with RMS seen at our institution from 2000-2015. The analysis was performed with JMP statistical software. Results: We identified 73 patients, with a median age of 51 (range 18-85 years). The majority of patients were male (40 of 73) and presented with localized disease (59 of 73). Histologic subtypes were as follows: 32% embryonal (E), 27% alveolar (A), 36% pleomorphic (P), and 6% variants (V) (botryoid and spindle cell/sclerosing). The median overall survival (OS) for patients with localized disease was 16.2 months and metastatic disease 9 months. The median OS for patients with localized disease treated with VAC was 20.3 months (4A, 7E, 3P) and VDC (vincristine doxorubicin cyclophosphamide) was 14.1 months (3A, 3E, 2P). For those with localized disease treated with a VAC/actinomycin-based chemotherapy had a median OS of 19.5 months (4A, 9E, 3P) and with a VDC/doxorubicin-based chemotherapy had a median OS of 15.9 months (8A, 5E, 13P, 2V). Conclusions: Adult patients with RMS have an even distribution among the histologic subtypes. Given the small, unbalanced number of patients in each histologic subtype treated with VAC/actinomycin-based or VDC/Doxorubicin-based regimens, the overall survival benefit favoring the use of VAC/actinomycin-based is hypothesis generating and confirmatory studies are needed to truly determine the optional regimen for adult patients with RMS.

Prognostic value of tumor response in pediatric and adult patients with Ewing sarcoma.

10543 Background: European Ewing sarcoma (ES) regimens use histologic response to chemotherapy at the time of local control to identify patients for treatment intensification. Prognostic importance of histologic response has not been confirmed in North American regimens and is currently under study in the most recent COG protocol. We aim to characterize histologic tumor response at time of local therapy in ES and correlate tumor response with patient outcomes. Methods: The Mayo Clinic tumor registry was used to retrospectively identify patients with non-metastatic ES from January 1977 to December 2012. Only patients who had neoadjuvant chemotherapy with surgery as the initial local control modality were included. Two pathologists reviewed stored surgical specimens and documented the percent necrosis and remaining viable tumor. A chart review collected demographic, treatment and outcome data. Results: Registry review identified 360 patients with ES, of which 87 met inclusion criteria. Median patient age was 15.7 years (range 2.4 – 54.5 years). Distribution of primary tumor sites included 66% extremity, 22% axial and 13% pelvic. Median time interval from diagnosis to surgery was 3.6 months (range 1.5-13.7 months). A vincristine, doxorubicin, cyclophosphamide (VDC) backbone was used in 97% of patients; 77% received VDC/IE (ifosfamide, etoposide). Median follow up was 6.6 years (range 0.38 – 36.1 years). Twenty-seven patients developed recurrence (31%); 3 local only, 19 distant only, 4 local and distant, and 1 unknown. The 5 year event-free survival (EFS) of patients with ≤ 5% viable tumor at the time of local control surgery compared to patients with > 5% viability was 76% and 59% respectively (p = 0.0141). The 5 year overall survival (OS) of these two groups was 83% and 62% respectively (p = 0.0146). When analysis was limited to patients treated with VDC/IE (n = 66), the trend was similar (5 year EFS of 80% vs 69%, p = 0.1907). Conclusions: Histological tumor response of ≤ 5% tumor viability at the time of local control surgery in pediatric and adult ES patients is associated with improved EFS and OS. Patients with greater than 5% viability are at an increased risk of recurrence and may benefit from treatment intensification.

Pilot Study of Adding Vincristine, Topotecan, and Cyclophosphamide to Interval-Compressed Chemotherapy in Newly Diagnosed Patients With Localized Ewing Sarcoma: A Report From the Children's Oncology Group

The combination of topotecan and cyclophosphamide is active in relapsed Ewing sarcoma family of tumors (ESFT). The feasibility of adding these agents combined with vincristine (vincristine-topotecan-cyclophosphamide [VTc]) to standard five-drug chemotherapy with vincristine-doxorubicin-cyclophosphamide (VDC) and ifosfamide-etoposide (IE) administered in an interval-compressed (2-week instead of 3-week intervals) schedule was investigated. Newly diagnosed patients with localized ESFT < 31 years, with good performance status and adequate organ function were eligible. Seventeen alternating cycles of chemotherapy with VTc, VDC, and IE were administered at 2-week intervals. Local control (LC) of the primary tumor occurred following six cycles. Primary endpoints were the ability to deliver chemotherapy in an interval-compressed schedule, and the rate of grade 3 or greater nonhematologic toxicity and grade 4 hematologic toxicity, which delayed chemotherapy by ≥2 weeks. Secondary endpoints were event-free survival (EFS) and overall survival (OS). Thirty-five patients with a median age of 11 years were enrolled. The mean time to last dose of chemotherapy prior to LC was 12.6 ± 1.4 weeks and 45.5% of patients received intended chemotherapy without any delay prior to LC. There were no toxic deaths or unexpected toxicities. Five-year EFS was 79.6% (95% confidence interval [CI]: 61.8-89.7%) and 5-year OS was 88% (95% CI: 71.4-95.3%). The addition of VTc to standard therapy was tolerable with sufficient interval compression compared to historical standard 3-week cycles.

A Case of Clear-Cell Sarcoma in the Stomach

Clear-cell sarcoma (CCS) is a rare soft tissue sarcoma that usually develops in the lower extremities of young adults. CCS of the gastrointestinal tract is extremely rare. We report here the first case of CCS of the stomach in Korea. A 28-year-old female developed a large tumor of the stomach that was initially considered Ewing sarcoma, based on the results of a needle biopsy. She had paraneoplastic syndrome; fever, anemia, and hyperglycemia. Follow-up abdominal computed tomography after four-cycles of chemotherapy with vincristine–doxorubicin–cyclophosphamide or ifosfamide–etoposide showed no tumor shrinkage and revealed a fistula between the tumor and the gastric lumen. The infected tumor prompted debulking surgery, which resulted in improvement of her symptoms. The pathologic findings were consistent with CCS, and fluorescence in situ hybridization for EWS gene rearrangement was positive, confirming the diagnosis. This case highlights the importance of clinical suspicion for CCS in chemotherapy-refractory Ewing sarcoma. (Korean J Med 2015;89:465-469)

Metastatic Malignant Transformation of Teratoma to Primitive Neuroectodermal Tumor (PNET)

Metastatic germ cell cancers are highly chemosensitive and have 80% cure rate with cisplatin-based chemotherapy. Postchemotherapy teratoma can usually be surgically resected. However, teratoma, which is pluripotent tissue, can undergo malignant transformation along mesodermal elements to primitive neuroectodermal tumor (PNET). Unlike teratoma, PNET can metastasize and render a patient unresectable and incurable. We report the results of treatment of patients with malignant transformation to PNET with cyclophosphamide+doxorubicin+vincristine (CAV) alternating with ifosfamide+etoposide (IE). We reviewed 86 patients with histologically confirmed PNET transformed from testicular teratoma at Indiana University from 1998 to 2012. We identified 18 patients who were treated with chemotherapy comprising cyclophosphamide (1000 to 1200 mg/m), doxorubicin (50 to 75 mg/m), and vincristine (2 mg) alternating with ifosfamide (1.8 g/m) plus etoposide (100 mg/m) for 5 consecutive days. Treatment was given every 3 weeks with a maximum of 6 cycles or until progression or undue toxicity. Hematopoietic growth factors were usually incorporated. The remaining 68 patients underwent surgical resection. Twelve patients had unresectable disease and 6 were treated in an adjuvant setting. Median age was 29 years (range, 20 to 53 y). Nine of the 12 metastatic patients achieved objective response by RECIST criteria. Six of those were rendered with no evidence of disease (NED) with further surgery. Although 4 of the 6 patients subsequently relapsed, 1 patient remains alive and NED at 78 months. The 6 patients who received adjuvant treatment are alive with NED at 9 to 90 months with a median duration of 32.7 months. CAV and IE alternating chemotherapy has high objective response rate for PNET transformed from teratoma and results in occasional long-term disease-free survival when combined with subsequent resection. We recommend adjuvant CAV alternating with IE chemotherapy for patients with PNET after RPLND due to the high probability of recurrent disease and their high chemosensitivity to this regimen.

Intra-patient dose escalation in Ewing’s sarcoma treated with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide: a retrospective review

BackgroundData suggests that males experience less toxicity and poorer survival than females treated for Ewing’s sarcoma. We instituted an intra-patient dose escalation (DE) policy with Vincristine/Doxorubicin/Cyclophosphamide (VDC) alternating with Ifosfamide/Etoposide (IE) based on hematological nadirs and report its feasibility and safety.MethodsA retrospective review of adherence to DE guidelines and toxicities was conducted for patients who received DE with VDC/IE over 3 years at a single cancer center. Absolute neutrophil counts (ANC) was collected on days 8, 12 and 15 for cycles 1–6. DE of 10%/cycle was applied if ANC > 1.5×109/L and platelet > 100×109/L on all blood results. The primary endpoint was the proportion of patients who received appropriate DE. The secondary endpoint was to assess morbidity, changes in hematologic nadirs between gender and age and a comparison with a prior cohort of ESFT patients who did not receive DE. Gender comparisons were assessed via independent 2-sample t-tests assuming unequal variances. Within cycle changes in hematologic nadirs were assessed using repeated measures ANOVA. Relapse free survival and overall survival (OS) curves were estimated using the Kaplan-Meier method.Results23 patients were identified (mean age: 27; range 17–54). 91 decisions for DE were made (1 decision excluded because of progressive disease) with 90% concordance with guidelines. No adverse outcomes occurred as a result of the inappropriate escalation. Grade 3/4 febrile neutropenia (FN) during VDC and IE was 26.1% (6/23 patients) and 17.4% respectively with no difference for those who were DE. Males were less neutropenic after C1 and C3 of VDC compared to females (P-value C1 = 0.003; C3 = 0.005). VDC was associated with greater neutropenia on day 8 whereas IE had greater neutropenia on day 12 (P-value <0.001). During VDC, a non statistical difference in neutropenia was seen for individuals aged 15–25 (n = 13) compared with older individuals (P-value = 0.09). OS comparison for those with localized disease with a prior cohort who were not DE showed similar outcomes (P-value = 0.37).ConclusionsDE is deliverable without increased adverse outcomes. Males have less myelosuppression during VDC, and should be especially considered for DE.

1525P - Third-Line Chemotherapy in Small Cell Lung Cancer: An International Analysis

ABSTRACT Background Small cell lung cancer (SCLC) is an aggressive disease and chemotherapy (CT) is the mainstay of treatment. Despite good response rates most patients (pts) will relapse and die of this disease. Standard 1st-line CT in limited (LD) and extensive stage disease is usually etoposide with platinum (P) or CAV (cyclophosphamide, doxorubicin, vincristine). At progression, 2nd-line CT may involve re-challenging with the 1st-line regimen. For pts who progress after 2 lines of CT, there is little evidence to guide treatment decisions, and the benefit of 3rd-line CT is unclear. Objective To determine the clinical benefit of 3rd-line CT for SCLC. Study design An international multi-centre retrospective analysis of pts who received 3 lines of CT for SCLC from 2001-2011 was performed. Baseline demographics, known prognostic factors and CT details were recorded. The main end-points were response rate (RR) and overall survival (OS) after 3rd-line CT. Results A total of 124 eligible pts were identified; 59% male, median age 61, 89% ECOG 0-1, 40% LD. First-line P-based CT was given to 99% of pts, with a RR of 90%. In the 2nd-line, 70 pts (56%) were re-challenged with similar CT, with the remaining receiving either CAV or topotecan based CT, with an RR of 50%. In the 3rd-line, 35 pts (28%) were re-challenged with CT similar to a prior regimen. Only 27 pts (22%) received 3 distinct lines of CT. Median progression free survival (PFS) in the 1st, 2nd and 3rd-lines were: 9.0, 4.6 and 2.0 months respectively. The RR in the 3rd-line was 17%, with no complete responses. Median 3rd-line OS was 4.8 months. Factors associated with longer OS were: normal baseline serum LDH (p = 0.02), response to 2nd-line CT (p = 0.04) and PFS >3 months after 2nd-line CT (p = 0.05). Age, sex, initial disease stage, and CT re-challenges did not predict longer survival. After the 3rd-line, 35 pts received further CT. Conclusions In 5 cancer centres, over 10 years, few SCLC pts received 3 lines of CT. Most who received 3 lines had been re-challenged with a similar regimen at least once. OS and RR in the 3rd-line are modest. Lack of response to, or progression after 2nd-line CT may predict particular lack of benefit in the 3rd-line. Prospective research in this area is needed. Disclosure All authors have declared no conflicts of interest.

Metastatic malignant transformation of teratoma to primitive neuroectodermal tumor (PNET): Results with PNET-based chemotherapy.

4598 Background: Metastatic germ cell cancers are highly chemosensitive and have 80% cure rate with cisplatin based chemotherapy. Post-chemotherapy teratoma can usually be surgically resected. However, teratoma, which is pleuripotent tissue, can undergo malignant transformation along mesodermal elements to PNET. Unlike teratoma, PNET can metastasize and render a patient unresectable and incurable. We report the results of treatment of patients with PNET with cyclophosphamide + doxorubicin + vincristine (CAV) alternating with ifosfamide + etoposide (IE). Methods: We reviewed 81 patients with histologically confirmed PNET transformed from testicular teratoma at Indiana University from 1998 to 2011. We identified 13 cases who were treated with chemotherapy comprising cyclophosphamide 1000-1200 mg/m2, doxorubicin 50-75 mg/m2, and vincristine 2 mg alternating with ifosfamide 1.8 grams/m2 plus etoposide 100 mg/m2 for 5 days. Treatment was given every 3 weeks with a maximum of 6 cycles or until progression or undue toxicity. Hematopoeitic growth factors were usually incorporated. The remaining 68 patients underwent surgical resection. Results: Ten patients had unresectable disease and 3 were treated in an adjuvant setting. Median age was 31 years (range 20-53). Ten of 13 patients had received prior platinum based chemotherapy. Eight of 10 evaluable patients achieved objective response. Five of those were rendered with no evidence of disease(NED) with further surgery. Although 4 of the 5 patients subsequently relapsed, 1 patient remains alive with NED at 69 months. The 3 patients who received adjuvant treatment after retroperitoneal lymph node dissection (RPLND) are alive with NED at 1, 4 and 8 years. Conclusions: CAV and IE alternating chemotherapy has high objective response rate for PNET transformed from teratoma and results in occasional long term disease free survival when combined with subsequent resection. We recommend adjuvant CAV alternating with IE chemotherapy for patients with PNET after RPLND due to the high probability of recurrent disease and their high chemosensitivity to this regimen.

Rare Non-Wilms’ Tumors in Children

We report our institutional experience of the management of 2 cases of rare non-Wilms' tumors; a rhabdoid tumor in a 17-month old boy and a clear cell sarcoma in a 5-year old girl. The two patients were treated with ifosfamide/carboplatin/etoposide (ICE) alternating with vincristine/doxorubicin/cyclophosphamide (VDC) and cyclophosphamide/etoposide (CE) alternating with vincristine/doxorubicin/cyclophosphamide (VDC) and radiotherapy, respectively. Both patients showed full response with no significant adverse events. At 2-year follow up, they are disease and relapse free. Although contemporary treatment regimens are very promising, multicenter collaborative studies are needed in order to define a standard treatment for non-Wilms' tumors.

Primary lung sarcoma: A review of 25 cases in a single tertiary institution.

e20528 Background: Primary lung mesenchymal tumours are quite rare occurring in <1% of all lung cancers (LC). Data is limited regarding the pathophysiology, natural history and treatment of these heterogeneous neoplasms. Treatment options are based on experience from other primary sarcomas. Methods: Medical records of 2,560 patients (pts) diagnosed with LC between 2003-2011 were screened. We examined pts’ demographics, clinical data and treatment details Results: 25/2,560 pts (1%) were diagnosed with primary mesenchymal lung tumours. Male:female ratio was 17:8 and median age 63 years (range 21-81). The histological subtypes as reported were: synovial sarcoma (n=9), Ewing’s Sarcoma/PNET (n=3), sarcomatous carcinoma (n=3), mesenchymal tumours/sarcoma (n=3), fibrosarcoma (n=2), malignant fibrous histiocytoma (n=1), leiomyosarcoma (n=1), blastoma (n=1), biphasic sarcoma (n=1) and polymorphic sarcoma (n=1). Immunocytochemistry showed overexpression of vimentin in 23 pts and of CD99 in 8 pts. Commonest presenting symptoms were chest pain (n=11) and dyspnoea (n=10). Performance Status was satisfactory (ECOG 0-1) in most pts (n=17). Smoking history was reported by 17/25 pts. 15 pts presented with advanced disease and were treated with chemotherapy (CT) (group A). 10 pts with initially localised disease (group B) were treated with either surgery (n=8) or radical chemoradiotherapy (CRT) (n=2). 4 pts received adjuvant CT. The commonest first line regimens were CAV (Cyclophosphamide, Doxorubicin, Vincristine) (n=10, 4pts with SD as best response) and platinum based combinations (n=7, best response: 1 PR, 3 SD). Median overall survival (OS) by Kaplan-Meier estimator for group A and group B were 6.5 months (95% CI 0.0-16.2) and 26 months (95% CI 23.8-28.2) respectively, with 2 pts of group A still on CT. Conclusions: Primary lung sarcoma is rare, occurring in approximately 1% of primary LC. OS in advanced disease is limited to less than 1 year. Surgery and radical CRT, when appropriate, are associated with better survival. Platinum agents seem active and warrant further prospective evaluation in this disease.

Nonmelanoma Skin Cancer

Nonmelanoma Skin Cancer

Results of Surgical Treatment for Patients with Small Cell Lung Cancer

This study investigated the clinical features and the postoperative prognosis in patients with small cell lung cancer (SCLC). In this study, 1373 patients underwent a resection of lung cancer between 1980 and 2006. There were 53 patients (3.8%) with SCLC among them. They were divided into two groups, including the early (1980-1993) and late (1994-2004) period groups. The clinicopathologic features and the results of surgery were investigated. The early and late period groups consisted of 22 and 31 patients, respectively. The pathologic stage of early group was stage IA in five, IB in three, II in five, IIIA in five, and IIIB in four patients and of late group was stage 0 in two, IA in three, IB in three, II in seven, IIIA in nine, and IIIB in seven patients. The survival rates 5 years after surgery were 8.7 and 38.3%, respectively. Preoperative chemotherapy with CAV (cyclophosphamide, doxorubicin, vincristine) or PE (cis-diamminedichloroplatinum + VP16) regimens was performed in 11 patients in the early period group. The treatment response was evaluated as a partial response in eight patients and stable disease in three. In the late period group, cis-diamminedichloroplatinum/carboplatin + VP16 therapies were administered to eight patients. The treatment response was evaluated as a complete response in two patients and partial response in six. Surgery could be performed with a curative intent in only a small number of patients with limited disease of SCLC or significant nodal response after chemotherapy. The prognosis after surgery was not satisfactory, especially in the early period. It was considered to be partly because of differences in the regimens and dose intensity of chemotherapy between the early and late period.

Primary Non-Hodgkin Lymphoma of Liver

Primary non-Hodgkin lymphoma (NHL) of liver is a very rare malignancy. Here, we report the case of a 65-year-old man who presented with constipation and right groin pain of 2 months' duration. A computed tomography (CT) scan of the abdomen incidentally detected multiple hypodense nodules in both lobes of the liver. Diagnosis of primary NHL of liver was made using ultrasound-guided biopsy. Extensive investigations--which included bone marrow biopsy; fluorescence in situ hybridization; flow cytometry; CT scan of chest, abdomen, and pelvis; and whole-body positron-emission tomography--showed no involvement of bone marrow, lymph nodes, spleen, or any other organ. The patient is currently being treated with a CHOP-R (cyclophosphamide-doxorubicin-vincristine-prednisolone/rituximab) regimen. The case has many unique features, including normal liver function tests, especially that for lactate dehydrogenase; no type B symptoms; and negative serology for viruses. The case demonstrates that primary hepatic lymphoma should be considered in the differential diagnosis of space-occupying liver lesions in presence of normal levels of alpha-fetoprotein and carcinoembryonic antigen. The literature is extensively reviewed.