Embryonal Rhabdomyosarcoma

Ballard, Karen S.; Tedjarati, Sean S.; Robinson, William R.; Homesley, Howard D.; Thurston, Erin L.

doi:10.1111/igc.0b013e3181d320dd

Cited by 5 publications

(7 citation statements)

References 13 publications

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“…Many attempts have been made over the years to develop an ex vivo anticancer test that can provide clinically relevant treatment information. However, until now, this approach has been hampered by the chemotherapy testing only being performed on bulk of tumor cells derived from cancer biopsies [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] . GBMs contain a heterogeneous population of cells, among which is a population of self-renewing cancer stem cells (CSCs) that contribute to tumorigenesis, treatment resistance, and tumor recurrence [3] , [6] .…”

Section: Introductionmentioning

confidence: 99%

Analysis of Chemopredictive Assay for Targeting Cancer Stem Cells in Glioblastoma Patients

Howard

Valluri

Alberico

et al. 2017

Translational Oncology

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Introduction: The prognosis of glioblastoma (GBM) treated with standard-of-care maximal surgical resection and concurrent adjuvant temozolomide (TMZ)/radiotherapy remains very poor (less than 15 months). GBMs have been found to contain a small population of cancer stem cells (CSCs) that contribute to tumor propagation, maintenance, and treatment resistance. The highly invasive nature of high-grade gliomas and their inherent resistance to therapy lead to very high rates of recurrence. For these reasons, not all patients with similar diagnoses respond to the same chemotherapy, schedule, or dose. Administration of ineffective anticancer therapy is not only costly but more importantly burdens the patient with unnecessary toxicity and selects for the development of resistant cancer cell clones. We have developed a drug response assay (ChemoID) that identifies the most effective chemotherapy against CSCs and bulk of tumor cells from of a panel of potential treatments, offering great promise for individualized cancer management. Providing the treating physician with drug response information on a panel of approved drugs will aid in personalized therapy selections of the most effective chemotherapy for individual patients, thereby improving outcomes. A prospective study was conducted evaluating the use of the ChemoID drug response assay in GBM patients treated with standard of care. Methods: Forty-one GBM patients (mean age 54 years, 59% male), all eligible for a surgical biopsy, were enrolled in an Institutional Review Board–approved protocol, and fresh tissue samples were collected for drug sensitivity testing. Patients were all treated with standard-of-care TMZ plus radiation with or without maximal surgery, depending on the status of the disease. Patients were prospectively monitored for tumor response, time to recurrence, progression-free survival (PFS), and overall survival (OS). Odds ratio (OR) associations of 12-month recurrence, PFS, and OS outcomes were estimated for CSC, bulk tumor, and combined assay responses for the standard-of-care TMZ treatment; sensitivities/specificities, areas under the curve (AUCs), and risk reclassification components were examined. Results: Median follow-up was 8 months (range 3-49 months). For every 5% increase in in vitro CSC cell kill by TMZ, 12-month patient response (nonrecurrence of cancer) increased two-fold, OR = 2.2 (P = .016). Similar but somewhat less supported associations with the bulk tumor test were seen, OR = 2.75 (P = .07) for each 5% bulk tumor cell kill by TMZ. Combining CSC and bulk tumor assay results in a single model yielded a statistically supported CSC association, OR = 2.36 (P = .036), but a much attenuated remaining bulk tumor association, OR = 1.46 (P = .472). AUCs and [sensitivity/specificity] at optimal outpoints (>40% CSC cell kill and >55% bulk tumor cell kill) were AUC = 0.989 [sensitivity = 100/specificity = 97], 0.972 [100/89], and 0.989 [100/97] for the CSC only, bulk tumor only, and combined models, respectively. Risk categorization of patients w...

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Section: Introductionmentioning

confidence: 99%

Analysis of Chemopredictive Assay for Targeting Cancer Stem Cells in Glioblastoma Patients

Howard

Valluri

Alberico

et al. 2017

Translational Oncology

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“…The frequency of uRMS subtypes in adult women is unknown, the reports of gynecological RMS concluded that the most common RMS subtypes involving the uterus are uERMS, followed by PRMS, and ARMS [ 2 , 3 , 4 , 5 , 6 , 34 , 35 , 36 ]. The final diagnosis is made on histological evaluation of the biopsy or operative specimen, in combination with an IHC examination [ 1 , 4 , 5 , 6 , 12 , 37 , 38 ]. ERMS tumor cells are characterized by a small and fusiform nucleus.…”

Section: Discussionmentioning

confidence: 99%

“…On the histological examination, attention should also be paid to the differential diagnosis between the uRMS and adenosarcoma, carcinosarcoma, endometrial stromal sarcoma, or leiomyosarcoma because some of these entities can occasionally reveal skeletal muscle differentiation [ 1 , 5 , 6 ]. In accordance with the large case series from Ferguson et al [ 1 ] and Li et al [ 5 ], our case and nearly all tumors identified in the published case reports with histopathological (HP) detail, are positive for myogenin (93.8%) and desmin (98%), and negative for hormone receptors [ 1 , 5 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 24 , 25 , 26 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. The Ki-67 index or the mitotic index, is usually high, but was only evaluated in 20% of patients and we cannot draw any conclusions related to clinical aggressiveness of the tumor [ 5 , 11 , 15 , 16 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…In accordance with the large case series from Ferguson et al [ 1 ] and Li et al [ 5 ], our case and nearly all tumors identified in the published case reports with histopathological (HP) detail, are positive for myogenin (93.8%) and desmin (98%), and negative for hormone receptors [ 1 , 5 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 24 , 25 , 26 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. The Ki-67 index or the mitotic index, is usually high, but was only evaluated in 20% of patients and we cannot draw any conclusions related to clinical aggressiveness of the tumor [ 5 , 11 , 15 , 16 , 37 , 38 ]. The microscopic findings of published uERMS with HP detail are summarized in Table 1 .…”

Section: Discussionmentioning

confidence: 99%

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Uterine embryonal rhabdomyosarcoma in adult women: a case report on the challenging diagnosis and treatment

Pop¹,

Stanciu-Pop²,

Jungels³

et al. 2023

Rom J Morphol Embryol

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Background: Uterine embryonal rhabdomyosarcoma (uERMS) in adult women is a very rare malignant entity. The study aim was to report a case of adult uERMS and to discuss the implications of histopathological diagnosis on the treatment and prognosis. Case presentation: We present here the clinicopathological features of a uERMS case in an adult woman. The study has been approved by the institutional Ethics Committee and an informed consent has been obtained (IJB/CE3005). A 45-year-old woman presented to her gynecologist with intermenstrual bleedings and polypoid cervical mass (initially interpreted as benign polyp). A second biopsy was sent to our Department of Pathology at the Jules Bordet Institute, Brussels, Belgium for revision and was reinterpreted as botryoid-type uERMS. The patient underwent a total hysterectomy. The final pathology confirms a 3 cm cervical ERMS, and a simple surveillance was decided by our multidisciplinary team. Six months later, pelvic magnetic resonance imaging control showed a recurrence in the right pelvic lymph nodes. Multi-drug chemotherapy and radiotherapy were done before surgical resection. Pathological examination of the resected pelvic mass confirmed uERMS recurrence of 60 mm, with large zones of necrosis and the presence of cartilaginous structures. The patient is free of disease 60 months after diagnosis. Conclusions: Adult uERMS is rare and the pathological examination is the main element for diagnosis and treatment. It is often confused with other benign entities, at least at the time of diagnosis. ERMS should be included in the differential diagnosis of cervical and uterine polyp of adult women. Long-term survival is possible with a multimodal therapy approach.

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“…In the recent past, chemotherapy testing has been performed on cancer cells from patients without prior separation and enrichment of the CSLCs from the bulk of tumor cells [30], [36]–[45].…”

Section: Discussionmentioning

confidence: 99%

Chemo-Predictive Assay for Targeting Cancer Stem-Like Cells in Patients Affected by Brain Tumors

et al. 2014

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Administration of ineffective anticancer therapy is associated with unnecessary toxicity and development of resistant clones. Cancer stem-like cells (CSLCs) resist chemotherapy, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for individualized anticancer treatments. We have developed an ex vivo chemotherapy sensitivity assay (ChemoID), which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents. Two patients, a 21-year old male (patient 1) and a 5-month female (patient 2), affected by anaplastic WHO grade-III ependymoma were screened using the ChemoID assay. Patient 1 was found sensitive to the combination of irinotecan and bevacizumab, which resulted in a prolonged disease progression free period of 18 months. Following recurrence, the combination of various chemotherapy drugs was tested again with the ChemoID assay. We found that benzyl isothiocyanate (BITC) greatly increased the chemosensitivity of the ependymoma cells to the combination of irinotecan and bevacizumab. After patient 1 was treated for two months with irinotecan, bevacizumab and supplements of cruciferous vegetable extracts containing BITC, we observed over 50% tumoral regression in comparison with pre-ChemoID scan as evidenced by MRI. Patient 2 was found resistant to all treatments tested and following 6 cycles of vincristine, carboplatin, cyclophosphamide, etoposide, and cisplatin in various combinations, the tumor of this patient rapidly progressed and proton beam therapy was recommended. As expected animal studies conducted with patient derived xenografts treated with ChemoID screened drugs recapitulated the clinical observation. This assay demonstrates that patients with the same histological stage and grade of cancer may vary considerably in their clinical response, suggesting that ChemoID testing which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents could lead to more effective and personalized anticancer treatments in the future.

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Embryonal Rhabdomyosarcoma

Cited by 5 publications

References 13 publications

Analysis of Chemopredictive Assay for Targeting Cancer Stem Cells in Glioblastoma Patients

Analysis of Chemopredictive Assay for Targeting Cancer Stem Cells in Glioblastoma Patients

Uterine embryonal rhabdomyosarcoma in adult women: a case report on the challenging diagnosis and treatment

Chemo-Predictive Assay for Targeting Cancer Stem-Like Cells in Patients Affected by Brain Tumors

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