Partial response to erlotinib in a patient with imatinib-refractory sacral chordoma

Background Chordoma is a rare, slow growing and locally aggressive mesenchymal neoplasm with uncommon distant metastases. It is a chemo-resistant disease with surgery and radiotherapy being the mainstay in treatment of localized disease. In advanced disease imatinib has a role. We report a case of metastatic sacral chordoma with symptomatic and radiological response to erlotinib post-progression on imatinib. Case presentation A 48-year-old male with a sacral chordoma underwent partial sacrectomy followed by post-operative radiotherapy. Upon recurrence he received palliative radiotherapy to hemipelvis and was offered therapy with imatinib. However, the disease was refractory to imatinib and he was started on treatment with erlotinib—showing a partial response on imaging at two months. He is currently doing well at 13 months since start of erlotinib. Conclusions As seen in previously reported cases, erlotinib is a therapeutic option in advanced chordoma, even in imatinib refractory cases and thus warrants exploration of its therapeutic role in prospective clinical trials.

Locally recurrent extraskeletal myxoid chondrosarcoma of the shoulder: a case of complete neoadjuvant radiotherapy response

Background Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue tumor that typically affects the lower limbs of men between the ages of 50 and 60. EMC of the shoulder is rare with a high risk of local recurrence and distant metastasis. A planned surgical excision in sarcoma referral centers (SRCs) is mandatory to obtain the best outcome. The role of chemotherapy (CHT) and Radiotherapy (RT) on soft tissue chondrosarcoma is still controversial. Case presentation A 47-year-old man presented to our referral center with a history of EMC in the right shoulder excised with microscopic positive surgical margins in a non-referral center. Staging imaging exams did not reveal distant metastasis or residual disease, but during follow-up a local recurrence was detected. After a multidisciplinary discussion, preoperative radiotherapy was administered with a total dose of 50 Gy, and then the patient underwent wide surgical excision. Histological examination was negative for viable tumor cells. No relapse occurred in a 24-months post-operative follow up. Conclusions The case here described suggests the importance of patient’s management in SRCs. A planned combined treatments with both surgery and RT seems to be the best choice to improve local control. RT seems to be promising within this specific histotype. Further studies are needed to confirm if the observed efficacy of combined treatments reflects in a consistent survival benefit for EMC patients.

The role of prognostic nutritional index in the management of pulmonary sarcomatoid carcinoma

Background Pulmonary sarcomatoid carcinoma is characterized by poor survival rates compared with other non-small cell lung cancer. Prognostic nutritional index has significant prognostic value in many malignant tumors. We conducted this retrospective study to investigate the role of prognostic nutritional index in patients with pulmonary sarcomatoid carcinoma and to determine prognostic factors. Methods Of 8176 patients with resected lung cancer in a single high-volume institution between 2008 and 2015, 91 patients with pathologically diagnosed sarcomatoid carcinoma were included in our study and evaluated. Kaplan–Meier analysis and Cox regression analysis were conducted to analyze clinicopathologic data. Subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) among pulmonary sarcomatoid carcinoma patients were also conducted. Results Univariable analysis showed that tumor size (P = 0.018 in OS), and P = 0.021 in RFS), tumor stage(P < 0.001 in OS, and P = 0.002 in RFS), nodal metastasis (P < 0.001 in OS, and P < 0.001 in RFS), pathological stage (P < 0.001 in OS, and P < 0.001 in RFS), treatment modality (P = 0.032 in OS, and P = 0.059 in RFS) and PNI (P < 0.001 in OS, and P < 0.001 in RFS), were significant factors of both OS and RFS. In multivariable analysis, for OS, the pathological stage (Hazard ratio (HR) 1.432; 95% confidence interval (95% CI) 1.210–1.695; P < 0.001) and PNI (HR 0.812; 95% CI 0.761–0.865; P < 0.001) were independent prognostic factors. And for RFS, We found PNI as an independent prognostic factor (HR 0.792; 95% CI 0.739–0.848; P < 0.001), and the pathological stage (HR 1.373; 95% CI 1.160–1.625; P < 0.001). In the subgroup of patients with PNI ≥ 49.4, univariable analysis showed treatment modality was a significant factor of overall survival (P = 0.001); multivariable analysis showed patients received postoperative chemotherapy (HR 0.288; 95% CI 0.095–0.874; P = 0.028) or postoperative chemotherapy with targeted therapy (HR 0.148; 95% CI 0.030–0.726; P = 0.019) has better overall survival rates. Conclusion The PNI and the pathological TNM stage are independent prognostic factors for pulmonary sarcomatoid carcinoma. PNI is an important indicator for the selection of postoperative adjuvant therapy. Patients with PNI ≥ 49.4 may benefit from postoperative chemotherapy and targeted therapy. We still need further prospective studies to confirm these results.

Ifosfamide-induced encephalopathy: the EEG with frontal intermittent delta activity, and rapid resolution with methylene blue: A case report

Background Encephalopathy is an established side effect of the chemotherapeutic agent, ifosfamide, occurring in 10–30% of cases. The EEG commonly shows non-specific features of encephalopathy, and rarely shows frontal intermittent rhythmic delta activity (FIRDA). Case presentation This is a case report of a 71 year old woman with pleomorphic sarcoma, who developed ifosfamide-induced encephalopathy with her second dose of ifosfamide. It shows the characteristic EEG findings that have been described previously with ifosfamide-induced encephalopathy and additionally the unusual and rare finding of FIRDA. This was followed up by a further EEG showing resolution of the encephalopathy, after administration of methylene blue, coinciding with rapid and complete resolution of her symptoms. Conclusion The rapid resolution of the encephalopathy on the EEG after administration of methylene blue adds further evidence to its effectiveness as a treatment for the disorder.

Simultaneous diagnosis of liver PEComa in a family with known Li–Fraumeni syndrome: a case report

Background Li–Fraumeni syndrome (LFS) is an autosomal dominant hereditary disease. It is associated with the loss of function of the p53 protein and an increased risk of malignant tumor development at early age. The most frequently detected tumors include breast cancer, sarcomas, leukemia, brain tumors, and adrenocortical carcinomas. While sarcomas account for only 1% of solid tumors, they are more frequently detected in these families. Case presentation We report a simultaneous diagnosis of hepatic perivascular epithelioid cell tumor (PEComa), a very rare subtype of sarcoma, in two siblings with a LFS. Conclusions The simultaneous diagnosis of PEComa in two siblings presented in this case allowed us to review the frequency of PEComa in this genetic syndrome previously reported, which was very little. Despite its rarity, PEComa must be considered in the differential diagnosis of new-onset liver lesions in patients who were previously diagnosed with LFS.

Solitary extrapleural fibrous tumor with hepatic bilobar metastases: multimodal approach treatment

Background Solitary fibrous tumor is an unusual fibroblastic mesenchymal neoplasm typically described in the pleura. It may appear anywhere with a varied anatomic distribution and essentially it can develop from any soft tissue or visceral location. Its course is usually indolent and it rarely causes distant metastases, so it has a prolonged survival rate. It sometimes presents itself as a disseminate disease being the liver the most frequently involved location. In these occasions, the management should be discussed in a multidisciplinary tumor committee formed by surgeons, oncologists and radiologists. Surgery remains the gold standard for treatment. Case representation We present the case of a woman with a tumor in the left abdominal wall and bilobar massive liver metastases, both locations histologically diagnosed as solitary fibrous tumor. She receives biological treatment for a severe case of Crohn´s disease. Evaluated in a multidisciplinary committee, surgery was recommended for both the primary lesion and the liver metastases. The hepatobiliary surgeons considered a two-stage hepatectomy with portal vein embolization (PVE) as the best strategy. After the first procedure consisting in cleaning the left hepatic lobe followed by PVE the future liver remnant volume (FLRV) was considered inadequate, so the patient was also treated with right transarterial radioembolizacion with yttrium 90 (TARE-Y90) intending a double goal: to treat the tumor and to increased the FLRV. Furthermore, a severe flare of Crohn´s disease forced us to intensify the patient’s treatment with the addition of biological agents (infliximab and adalimumab) until complete remission of the symptoms. The second stage of the liver surgery had to be postponed for more than 6 months and could finally be carried out without complications, achieving an R0 resection. The postoperative course was uneventful and the follow up has showed no recurrence to date. Conclusion Solitary fibrous tumours with extensive liver metastases are infrequent but when they appear modern surgical strategies like two stage hepatectomy are the treatment of choice and must be carried out by specialised units. The therapeutic decisions should be guided by a multidisciplinary committee.

Preoperative accelerated radiotherapy combined with chemotherapy in a defined cohort of patients with high risk soft tissue sarcoma: a Scandinavian Sarcoma Group study

Background We recently reported outcomes from a Scandinavian Sarcoma Group adjuvant study (SSG XX group A) conducted on localized and operable high risk soft tissue sarcoma (STS) of the extremities and trunk wall. SSG XX, group B, comprised of patients in a defined cohort with locally advanced STS considered at high risk for intralesional surgery. These patients received preoperative accelerated radiotherapy, together with neoadjuvant and adjuvant chemotherapy. Herein we report the results of this group B. Methods Twenty patients with high-grade, locally advanced and deep STS located in lower extremities (n = 12), upper extremities (5) or trunk wall (3) were included. The median age was 59 years and 14 patients were males. The treatment regimen consisted of 6 cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2), with three cycles given neoadjuvantly, and preoperative radiotherapy (1, 8 Gyx2/daily to 36 Gy) between cycles 2 and 3. After a repeated MRI surgery was then conducted, and the remaining 3 chemotherapy cycles were given postoperatively at 3 weeks intervals. Survival data, local control, toxicity of chemotherapy and postoperative complications are presented. Results Median follow-up time for metastasis-free survival (MFS) was 2.8 years (range 0.3–10.4). The 5-year MFS was 49.5% (95% confidence interval [CI] 31.7–77.4). The median follow-up time was 5.4 years (range 0.3–10.4) for overall survival (OS). The 5-year OS was 64.0% (95% CI 45.8–89.4). The median tumour size was 13 cm, with undifferentiated pleomorphic sarcoma (n = 10) and synovial sarcoma (n = 6) diagnosed most frequently. All patients completed surgery. Resection margins were R0 in 19 patients and R1 in 1 patient. No patients had evidence of disease progression preoperatively. Three patients experienced a local recurrence, in 2 after lung metastases had already been diagnosed. Eleven patients (55%) had postoperative wound problems (temporary in 8 and persistent in 3). Conclusions Preoperative chemotherapy and radiotherapy were associated with temporary wound-healing problems. Survival outcomes, local control and toxicities were deemed satisfactory when considering the locally advanced sarcoma disease status at primary diagnosis. Trial registration This study was registered at ClinicalTrials.gov Identifier NCT00790244 and with European Union Drug Regulating Authorities Clinical Trials No. EUDRACT 2007-001152-39

Seeking international consensus on approaches to primary tumour treatment in Ewing sarcoma

Background The local treatment of Ewing sarcoma of bone involves surgery, radiotherapy or both. The selection of treatment depends on the anatomical extent of the tumour, the effectiveness of the proposed treatment, its morbidity, and the expectation of cure. However, not only are there variations in the approach to local treatment between individual patients, but also between treatment centres and countries. Our aim was to explore variation in practice and develop consensus statements about local treatment. Methods A three stage modified Delphi technique was used with international collaborators. This involved an expert panel to identify areas of controversy, an online survey of international collaborators and a consensus meeting in London, UK in June 2017. In the consensus meeting, teams of clinicians discussed the local management of selected cases and their responses were collected with electronic voting. Results Areas of greater or less consensus were identified. The lack of evidence underpinning different approaches was noted and areas for collaborative research became apparent. Conclusion This has demonstrated that there is an international consensus around many aspects of the local treatment of Ewing sarcoma of bone, including the use of specialist MultiDisciplinary Team (MDT) meetings with access to all appropriate treatments. However, considerable variation remains including the use of different staging investigations, decision making, definitions of response, and radiotherapy doses and timing. Further collaborative work should be undertaken to determine the impact of these variations in order to define best practice.

Glomus tumors with malignant features of the extremities: a case series

Background Malignant glomus tumors are exceedingly rare, however they can be locally aggressive and have the potential to metastasize. There is limited information available in the literature regarding treatment and outcomes, therefore we present a case series of 5 patients with glomus tumors with malignant features confined to the extremities that have presented to our tertiary sarcoma center within the last 20 years. This is the largest case series of its kind in the malignant glomus tumor literature, to our knowledge. Methods We performed a retrospective chart review of all patients with histologically confirmed glomus tumors with malignant features in the extremities found within the University of Michigan EMERSE database since January 1st, 2000. Results Five patients met our inclusion and exclusion criteria. Three patients were diagnosed with malignant glomus tumors, one patient with glomus tumor with uncertain malignant potential, and the last patient with malignant glomus tumor with leiomyosarcomatous features. Males and females were equally represented. Age range was 9–49 years at time of first presentation. All patients underwent an initial surgical resection. Three of the five patients (60%) underwent initial resection at an outside hospital prior to referral to tertiary sarcoma center, and all three required re-resection. One of these patients had local tumor recurrence after a planned positive margin resection and radiotherapy. Another patient had distant metastasis after a positive margin surgical resection and a short course of radiotherapy. All patients are still alive according to their medical record with the average time from initial treatment to last follow up of 59.2 months. Conclusions Our study supports the current literature that wide-local resection with the goal of negative margins is still the current gold standard treatment for glomus tumors with malignant features. Studies with larger cohorts are necessary before recommending for or against radiotherapy or chemotherapy. Early biopsy and referral to a tertiary sarcoma center prior to surgical resection may help reduce the re-resection rate and potential seeding of the tumor in these patients, thereby improving outcomes.