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Background The effectiveness of second‐line palliative chemotherapy in patients with recurrent/metastatic osteosarcoma is not well defined. Several small studies (6–19 patients) have reported on ifosfamide as second‐line treatment. In this study we report our single‐center experience with second‐line ifosfamide monotherapy in patients treated for recurrent/metastatic osteosarcoma. Methods A chart review was conducted of all patients with osteosarcoma treated with ifosfamide from 1978 until 2017. Until 1997 a 5 g/m2 regimen was used, and from 1997 onwards a 9 g/m2 regimen was used. Overall survival (OS) from start of ifosfamide was the primary endpoint. Progression‐free survival (PFS) from start of treatment was also studied. To assess difference in survival between groups the log rank test was applied. To investigate the effect of ifosfamide dose and World Health Organization performance status (PS) a Cox proportional hazard regression model was estimated. Results Sixty‐two patients were selected with recurrent/metastatic osteosarcoma treated with second‐line ifosfamide monotherapy (dose of 5 g/m2, n = 26; 9 g/m2, n = 36). OS was significantly better in univariate analysis for 9 g/m2 compared with 5 g/m2 (10.9 months [95% confidence interval (CI), 9.3–12.6] vs. 6.7 months [95% CI, 5.9–7.6], respectively) and for PS (median OS PS 0, 13.0 months [95% CI, 2.3–23.8]; PS 1, 8.2 months [95% CI, 5.4–11.1]; PS ≥2, 6.2 months [95% CI, 2.2–10.3]; and unknown PS, 5.4 months [95% CI, 2.2–8.5]). In multivariate analysis only PS showed a significant difference. No difference in PFS was found between 5 and 9 g/m2 ifosfamide treatment or PS. Conclusion This study suggests that ifosfamide is an effective second‐line treatment for patients with recurrent/metastatic osteosarcoma. Implications for Practice Ifosfamide monotherapy is commonly used as second‐line treatment in osteosarcoma, although large series to support this are lacking. This retrospective study reports overall and progression‐free survival for regimens with 5 g/m2 and with 9 g/m2. This study was unable to show a significant difference in survival between 5 and 9 g/m2 but showed an important impact of World Health Organization performance status on overall survival. This study sets a standard and reference for comparison with the multiple phase II studies under development., The effectiveness of second‐line palliative chemotherapy for recurrent or metastatic osteosarcoma has not been determined. This article reports the Leiden University Medical Center experience with ifosfamide monotherapy as palliative treatment in patients with osteosarcoma.

Lessons Learned Adjuvant treatment with zoledronic acid did not decrease the recurrence rate of giant cell tumor of bone (GCTB) in this study. The efficacy could not be determined because of the small sample size. GCTB recurrences, even in the denosumab era, are still an issue; therefore, a randomized study exploring the efficacy of zoledronic acid in the adjuvant setting in GCTB is still valid. Background Bisphosphonates are assumed to inhibit giant cell tumor of bone (GCTB)-associated osteoclast activity and have an apoptotic effect on the neoplastic mononuclear cell population. The primary objective of this study was to determine the 2-year recurrence rate of high-risk GCTB after adjuvant zoledronic acid versus standard care. Methods In this multicenter randomized open-label phase II trial, patients with high-risk GCTB were included (December 2008 to October 2013). Recruitment was stopped because of low accrual after the introduction of denosumab. In the intervention group, patients received adjuvant zoledronic acid (4 mg) intravenously at 1, 2, 3, 6, 9, and 12 months after surgery. Results Fourteen patients were included (intervention n = 8, controls n = 6). Median follow-up was long: 93.5 months (range, 48–111). Overall 2-year recurrence rate was 38% (3/8) in the intervention versus 17% (1/6) in the control group (p = .58). All recurrences were seen within the first 15 months after surgery. Conclusion Adjuvant treatment with zoledronic acid did not decrease the recurrence rate of GCTB in this study. The efficacy could not be determined because of the small sample size. Because recurrences, even in the denosumab era, are still an issue, a randomized study exploring the efficacy of zoledronic acid in the adjuvant setting in GCTB is still valid.

Objective: Suboptimal treatment of chemotherapy-induced nausea and vomiting and unsatisfactory response to antiemetic drugs cause impairment of cancer patient’s daily functioning. This study was aimed to investigate the association of selected germline polymorphisms with ondansetron and metoclopramide response in Indonesian cancer patients treated with highly emetogenic chemotherapy. Methods: We enrolled 202 chemotherapy nao¨ve patients treated with cisplatin at a dosage of � 50 mg/m 2 as monotherapy or as combined chemotherapy. Ondansetron 8 mg and dexamethasone 8 mg intravenously were the standard antiemetic therapy for prevention of acute chemotherapy-induced nausea and vomiting. Metoclopramide 10 mg orally, three times per day as fixed prescription, was given until 5 days after chemotherapy to prevent delayed chemotherapy-induced nausea and vomiting. Primary and secondary outcomes were the occurrence of chemotherapy-induced nausea and vomiting in the acute and delayed phase. The following single-nucleotide polymorphisms were determined in ABCB1: rs1045642, rs2032582 and rs1128503; in 5-HT3B-R: rs45460698, rs4938058 and rs7943062; and in CYP2D6: rs16947 (CYP2D6*2), rs3892097 (CYP2D6*4) and rs1065852 (CYP2D6*10 )u sing Taqman assays. Results: During the acute phase, 21.8 and 30.2% patients experienced Grade 3 and 4 nausea and vomiting, respectively, whereas 38.6% patients experienced nausea and/or vomiting in the delayed phase. Carriers of the CTG haplotype of the ABCB1 gene experienced Grade 3 and 4 chemotherapy-induced nausea and vomiting more often than other haplotypes in the delayed phase (P , 0.05). No associations were found with the 5-HT3B receptor haplotypes and CYP2D6-predicted phenotypes. Conclusions: Our study shows that in Indonesian cancer patients treated with highly cytostatic emetogenic, carriership of the CTG haplotype of the ABCB1 gene is related to an increased risk of delayed chemotherapy-induced nausea and vomiting.

A 39-year-old male patient with a favorable prognosis stage IIB metastatic malignant germ cell tumor (GCT) and elevated pre- and postorchiectomy serum human chorionic gonadotropin (hCG) was treated with three courses of combination chemotherapy resulting in a rapid normalization of his serum hCG. Within 2 months after the cessation of chemotherapy, his serum hCG increased again, suggesting tumor recurrence. Pathological examination of the resected residual retroperitoneal lymph nodes revealed no vital tumor cells. Based on the further rise in his serum hCG and enlargement of mediastinal lymph nodes on computed tomography scan, the patient underwent second- and third-line chemotherapy, which did not result in normalization of his serum hCG. Reanalysis of stored serum samples with other immunoassays revealed that the elevated serum hCG levels collected before first-line chemotherapy were indeed elevated, but those collected after first-line chemotherapy were all falsely positive. Currently, the patient is still alive and disease free. This is the first report of a male cancer patient who received unneeded second- and third-line chemotherapy for relapse based on false-positive hCG results. We discuss the pitfalls of false-positive serum hCG measurements, including heterophilic antibodies, as in our IgA-deficient patient, and review the literature.

ObjectiveAdrenal cortical carcinoma (ACC) is an aggressive tumour with a high mortality. We describe six patients living 12–28 years despite recurrent and/or metastatic ACC.PatientsThe first patient presented in 1979 with an ACC of 8 cm. After resection, she developed seven recurrences for which she was treated with resection and/or mitotane (o,p′-DDD) treatment. The patient is still alive 28 years after diagnosis. The second patient presented with an ACC of 9 cm. After resection, the patient developed liver metastases, which were treated witho,p′-DDD. The patient is still alive 25 years after diagnosis. The third patient presented with an ACC of 12 cm. The tumour was resected followed byo,p′-DDD treatment. She had a local recurrence that was completely resected. She is still alive 18 years after diagnosis. The fourth patient presented with an ACC of 14 cm. After resection, adjuvanto,p′-DDD was started. Subsequently, the patient developed two recurrences, which were resected. He is still alive 17 years after the initial diagnosis. The fifth patient presented with an ACC of 10 cm. After diagnosis, she developed lung metastasis, which were treated witho,p′-DDD and chemotherapy. The patient is still alive with slowly progressive disease 12 years after diagnosis. The sixth patient presented with an ACC of 7 cm. After resection, she developed four recurrences, which were resected. The patient is still alive 28 years after diagnosis.ConclusionSome patients can have an extremely long survival of ACC, despite recurrent disease and metastases. The mainstay of therapy in our patients was repeated surgery ando,p′-DDD.

BACKGROUND: Without active delivery across the blood-brain barrier, the efficacy of doxorubicin is limited in the treatment of brain tumors. 2B3-101 was developed as a brain-targeted doxorubicin product. In preclinical studies, 2B3-101 showed a 5-fold increased delivery of doxorubicin to the brain and improved survival of mice with HGG, compared to Caelyx®. METHODS: This open-label study assessed the safety, tolerability, MTD, PK and anti-tumor activity of 2B3-101. For this analysis, 30 HGG and 25 BCBM patients were included who received a 2B3-101 starting dose of 40-70 mg/m2 q21d (n = 35) or 60 mg/m2 q28d (n = 20 all HGG). Treatment continued until disease progression or unacceptable toxicity. Anti-tumor activity was assessed by RANO in HGG or RECIST 1.1 in BCBM patients. RESULTS: As of 30-May-2014, 172 cycles (range 1-10) of 2B3-101 were administrated, 4 HGG and 2 BCBM patients are still on treatment. 2B3-101 was tolerated up to a dose-intensity of 15 mg/m2/wk. Cycle 1 MTD was not reached. Phase 2a doses were selected based upon tolerability after repeated dosing. Most frequent reported treatment emergent AEs ≥ grade 2 were: neutropenia (41%), palmar-plantar erythrodysesthesia (PPE) (39%), fatigue (36%), stomatitis (21%), and infusion-reaction (20%). Notable grade 3–4 AEs were neutropenia (26%) and PPE (14%). All were transient and manageable with standard medication or dose delays. Dose reductions were required in 25% of the patients. 2B3-101 showed no neuro-or cardiotoxicity. In 25 evaluable HGG patients, 52% had SD as best response and 3-months PFS rate of 40%. 3 patients had intracranial response of ≥ 20%. In 23 evaluable BCBM patients, 9% had PR and 48% SD as overall best response with 3-months PFS rate of 48%. 4 patients had intracranial response of ≥ 20%. CONCLUSIONS: 2B3-101 is safe, well tolerated and shows promise as a potential treatment option for progressive HGG and BCBM patients.

Learning Objectives After completing this course, the reader will be able to: Classify the chondrosarcoma subtypes.Engage in the diagnostic process of chondrosarcoma.Evaluate the treatment options for chondrosarcoma. CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com This review provides an overview of the histopathology, classification, diagnostic procedures, and therapy of skeletal chondrosarcoma. Chondrosarcomas that arise de novo are primary chondrosarcomas, whereas chondrosarcomas developing superimposed on pre-existing benign cartilage neoplasms such as enchondromas or osteochondromas are referred to as secondary chondrosarcomas. Conventional chondrosarcomas can be categorized according to their location in bone into central, peripheral, and juxtacortical chondrosarcomas. Histological grading is related to prognosis; however, it is also subject to interobserver variability. Rare subtypes of chondrosarcoma, including dedifferentiated, mesenchymal, and clear cell chondrosarcoma, are discussed as well. Magnetic resonance imaging is necessary to delineate the extent of the intraosseous and soft tissue involvement preoperatively. Computed tomography is especially recommended in the pelvis and other flat bones where it may be difficult to discern the pattern of bone destruction and the presence of matrix mineralization. Wide, en-bloc excision is the preferred surgical treatment in intermediate- and high-grade chondrosarcoma. In low-grade chondrosarcoma confined to the bone, extensive intralesional curettage followed by local adjuvant treatment and filling the cavity with bone graft has promising long-term clinical results and satisfactory local control. Chondrosarcomas are relatively radiotherapy resistant; therefore, doses >60 Gy are needed in attempts to achieve local control after incomplete resection. Irradiation with protons or other charged particles seems beneficial in this curative situation. Chemotherapy is only possibly effective in mesenchymal chondrosarcoma, and is of uncertain value in dedifferentiated chondrosarcoma. Potential new systemic treatment targets are being discussed.

Envelope antigens of the Mason-Pfizer monkey virus (MPMV) and the morphologically similar HeLa virus, which is continuously produced in some HeLa cell lines, were compared by indirect immunoferritin techniques. Antisera raised against MPMV and HeLa virus revealed cross-reacting antigenic specificities on the surfaces of both agents, and cross-absorption and end-point dilution techniques indicated the presence of identical envelope antigens. The results demonstrated a close relationship, if not an identity, between MPMV and HeLa virus.