Twenty-year follow-up of osteosarcoma of the extremity treated with adjuvant chemotherapy

We have updated the results of an adjuvant chemotherapy study of 106 patients with osteosarcoma of the extremities published 17 years ago, treated by surgery followed by adjuvant chemotherapy with vincristine (VCR), methotrexate (MTX) and doxorubicin (ADM), between 1980-1983, and followed-up for at least 20 years (20-23 years). In comparison with the results reported 17 years ago with a median follow-up of 38 months (range: 27-66), this updated study showed 24 more deaths, 9 more relapses and 3 second malignancies. Consequently, event-free survival (EFS) and overall survival (OS) are significantly lower compared to the previous study with a 3-year follow up (EFS 38% vs 53%; OS 43.8% vs 67%). We conclude that osteosarcoma patients treated with chemotherapy are at risk of late adverse events. Protracted medical follow-up and long-term updated results are useful to identify, at an early stage, late relapses and late treatment-related complications.     

Neoadjuvant Chemotherapy for Osseous Malignant Fibrous Histiocytoma of the Extremity: Results in 18 Cases and Comparison with 112 Contemporary Osteosarcoma Patients Treated with the Same Chemotherapy Regimen

Abstract

Eigthteen patients with high grade malignant fibrous histiocytoma (MFH) of bone and 112 patients with high grade osteosarcoma (OS) of the extremity were treated with neoadjuvant chemotherapy comprised of methotrexate, cisplatinum, doxorubicin and ifosfamide. For the 18 patients with MFH, surgery involved amputation in 2 cases and limb salvage in 16 (89%); the 112 osteosarcoma patients had amputation in 8 cases and limb salvage procedure in 104 cases (93%). The rate of good histologic response to preoperative chemotherapy (90% or more tumor necrosis) was significantly higher in patients with osteosarcoma than in patients with MFH (74% vs 28%; p<0.003). However, at a median follow-up of 38 months (range 25-61), the 3-year event-free survival (EFS) did not differ in the two groups (MFH 77.8%, OS 70.5%; p=ns). In patients with MFH, no local recurrences were registered, whereas in the osteosarcoma group there were 6 local relapses (5.%).

The effectiveness of neoadjuvant chemotherapy in the treatment of osteosarcoma has been assessed during the last 15 years. The results of the present study seem to indicate that, in spite of a usually poor histologic response to preoperative treatment, neoadjuvant chemotherapy is very effective also in MFH of bone.     

Adjuvant and neoadjuvant chemotherapy for osteosarcoma of the extremities: 27 year experience at Rizzoli Institute, Italy

Around 1148 patients with non-metastatic osteosarcoma of the extremity were treated in a single institution between 1972 and 1999 with 4 different protocol of adjuvant and 7 different protocols of neoadjuvant chemotherapy. The rate of limb salvage increased from 20% to 71%. The 5-year event-free survival (EFS) and overall survival (OS) were 57% and 66%, respectively. The 10-year EFS and OS were 52% and 57%, respectively, and the results significantly correlated with serum alkaline phosphatase levels; the type of chemotherapy (adjuvant vs neoadjuvant); and with histologic response to pre-operative treatment. Aggressive chemotherapy and surgery could cure about the 60% of patients with osteosarcoma of the extremity. However, since local or systemic relapses, myocardiopathies and a second malignancy are possible even 5 or more years since the beginning of treatment, a long-term follow-up is recommended.     

Treatment of Adults and Young Adults with Acute Lymphoblastic Leukemia: Real Life Data from Two Centers in Slovakia

IntroductionThe results of treatment of acute lymphoblastic leukemia (ALL) from the low population countries are missing in the literature.Patients and methodsWe retrospectively examined biological characteristics and survival of 90 patients with ALL.ResultsAt median follow-up 17 months, 52 men and 38 women were eligible for the analysis with median age 43 years (18–74). As for the risk stratification, 25.6% of patients were in standard risk, 46.7% in high risk and 27.8% in very high-risk group. Complete remission achieved 88.9% of patients. We observed 5.6% of induction deaths and 4.5% of resistant disease. 47.8% of the patients underwent allogeneic stem cell transplantation (alloSCT), 59% in the young adults (YA; < 40 years) and 40% in adult group (≥ 40 years). We noticed 32.6% relapses overall with median survival of relapsed patients 3.9 months. YA patients had longer survival than adults: 3-year overall survival (OS) 65.0% vs 30.2%; (HR = 0.36; 95% CI 0.2–0.64; P = .001) and event free survival (EFS) 51.5% vs 21.9%; (HR = 0.45; 95% CI 0.26–0.78; P = .005). There was significant difference in 3-year EFS between risk groups in YA patients 90.9%, 48.0%, 11.4%; (P = .001). OS after alloSCT individually for the YA was 62.6% and for adults 39.1%, hazard ratio (HR) = 0.49 (95% CI 0.20–1.21); (P = .095). We observed 14% early deaths, 25.6% late deaths and 3 relapses (7%) after allogeneic stem cell transplantation.ConclusionsOur data proved that even in a low population country similar result can be achieved as in larger ones while using well designed adapted protocols from leukemic study groups.     

Adjuvant and neo-adjuvant chemotherapy for Ewing's sarcoma family tumors and osteosarcoma of the extremity: further outcome for patients event-free survivors 5 years from the beginning of treatment.

BACKGROUND: In 326 patients with Ewing's sarcoma family tumor (ESFT) and 628 extremity osteosarcoma (OS) treated with adjuvant and neo-adjuvant chemotherapy and event-free survivors 5 years from the beginning of treatment we evaluated outcome in the following years. Post 5-year follow-up for these patients was 9.7 years (5.5-29 years). PATIENTS AND METHODS: Adverse events observed after 5-year follow-up were 73 (7.6%): 38 late relapses, nine leukemia, 14 second solid tumor, seven radioinduced sarcoma, three severe adriamycin-related cardiomyopathy, one suicide and one death by car crash. RESULTS: Of the patients who developed late events, 16 (22.5%) are alive and event free after 8 years from the last treatment (2-22 years). CONCLUSION: We conclude that the high rate of late adverse events after 5 years in patients with OS and ESFT is noteworthy and indicates that these patients should be followed for >5 years.     

The clinical impacts of postoperative complications after colon cancer surgery for the clinical course of adjuvant treatment and survival

Aim

We investigated whether or not postoperative complications (POCs) themselves have a negative survival impact or indirectly worsen the survival due to insufficient adjuvant chemotherapy in a pooled analysis of two large phase III studies performed in Japan

Patients and methods

The study examined the patients who enrolled in 1304, phase III study comparing the efficacy of 6 and 12 months of capecitabine as adjuvant chemotherapy for stage III colon cancer patients and in 882, a phase III study to confirm the tolerability of oxaliplatin, fluorouracil, and l-leucovorin in Japanese stage II/III colon cancer patients. In our study, POCs were defined as the following major surgical complications: anastomotic leakage, pneumonia, bowel obstruction/ileus, surgical site infection, postoperative bleeding, urinary tract infection, and fistula. Patients were classified as those with POCs (C group) and those without POCs (NC group).

Results

A total of 2095 patients were examined in the present study. POCs were observed in 169 patients (8.1%). The overall survival (OS) rates at 5 years after surgery were 75.3% in the C group and 86.5% in the NC group (p = 0.0017). The hazard ratio of POCs for the OS in multivariate analysis was 1.70 (95% confidence interval, 1.19 to 2.45; p = 0.0040). The time to adjuvant treatment failure (TTF) of adjuvant chemotherapy was similar between the groups, being 68.6% in the C group and 67.1% in the NC group for the 6-month continuation rate of adjuvant chemotherapy. The dose reduction rate of adjuvant chemotherapy and adjuvant treatment suspension rate were also similar between the groups (C vs. NC groups: 45.0% vs. 48.7%, p = 0.3520; and 52.7% vs. 55.0%, p = 0.5522, respectively).

Conclusion

POCs were associated with a poor prognosis but did not affect the intensity of adjuvant chemotherapy. These results suggested that POCs themselves negatively influence the survival.

     

Extraskeletal Ewing Sarcomas in Late Adolescence and Adults: A Study of 37 Patients

Background: Extraskeletal Ewing sarcoma (EES)/primitive neuroectodermal tumours (PNET) are raresoft tissue sarcomas. Prognostic factors and optimal therapy are still unconfirmed. Materials and Methods:We performed a retrospective analysis on patients to explore the clinic characteristics and prognostic factorsof this rare disease. A total of 37 patients older than 15 years referred to our institute from Jan., 2002 to Jan.,2012 were reviewed. The characteristics, treatment and outcome were collected and analyzed. Results: Themedian age was 28 years (range 15-65); the median size of primary tumours was 8.2 cm (range 2–19). Sixteenpatients (43%) had metastatic disease at the initial presentation. Wide surgical margins were achieved in 14 cases(38%). Anthracycline or platinum-based chemotherapy was performed on 29 patients (74%). Radiotherapy wasdelivered in 13 (35%). At a median follow-up visit of 24 months (range 2–81), the media event-free survival (EFS)and overall survival (OS) were 15.8 and 30.2 months, respectively. The 3-year EFS and OS rates were 24% and43%, respectively. Metastases at presentation and wide surgical margins were significantly associated with OSand EFS. Tumour size was significantly associated with OS but not EFS. There were no significant differencesbetween anthracycline and platinum based chemotherapy regarding EFS and OS. Conclusions: EES/PNET is amalignant tumour with high recurrence and frequent distant metastasis. Multimodality therapy featuring widesurgical margins, aggressive chemotherapy and adjuvant local radiotherapy is necessary for this rare disease.Platinum-based chemotherapy can be used as an adjuvant therapy.     

Autologous Hematopoietic Cell Transplantation Versus Chemotherapy Alone for Immunoglobulin Light Chain Amyloidosis: A Retrospective Study

IntroductionImmunoglobulin light chain (AL) amyloidosis is caused by the deposition of monoclonal immunoglobulin light chains, for which autologous hematopoietic cell transplantation (AHCT) is one of the most effective therapies. In small studies comparing AHCT with chemotherapy alone, AHCT was associated with better survival.Patients and MethodsIn this study, we compared the outcomes of AHCT with those of chemotherapy alone in 232 patients. We retrospectively reviewed the outcomes in 74 patients who underwent AHCT with those of 158 patients treated only with chemotherapy.ResultsThe median event-free survival (EFS) (73 vs. 9 months; P < .001) and overall survival (OS) (not achieved vs. 39 months; P < .001) were superior in the AHCT group versus those in the chemotherapy group. On multivariate analysis, AHCT was significantly associated with better EFS (hazard ratio, 0.410; 95% confidence interval, 0.241-0.697; P = .0010) and OS (hazard ratio, 0.313; 95% confidence interval, 0.155-0.636; P = .0013) than chemotherapy alone. Even when patients with severe findings (mean left ventricular thickness > 12 mm, brain natriuretic peptide level > 400 pg/mL, and creatinine level > 2.0 mg/dL) and elderly patients (age > 65 years) were excluded, both EFS and OS were significantly better in the AHCT group than in the chemotherapy group upon univariate and multivariate analyses.ConclusionAHCT yielded better EFS and OS than chemotherapy alone in patients with AL amyloidosis. AHCT should be considered for eligible patients.     

Surgical outcomes and prognostic factors of non-metastatic radiation-induced sarcoma of bone

BackgroundThe survival and prognostic factors in non-metastatic, radiation-induced bone sarcomas of bone have not been described. Moreover, the quantitative data about surgical outcomes and complications after limb-salvage surgery versus amputation are quite limited.MethodsTwenty-five patients with non-metastatic, radiation-induced sarcoma of bone who underwent definitive surgery were analysed. Histological diagnosis was osteosarcoma in 19 and undifferentiated pleomorphic sarcoma in six. The definitive surgery was limb-salvage surgery in 15 patients and an amputation in 10.ResultsThe 5-year overall survival rate (OS) and the 5-year event-free survival rate (EFS) were 53% (95% CI 31%–70%) and 40% (21%–59%), respectively. Patients with wide or radical surgical margins (n = 13) showed significantly better OS compared with those with marginal (n = 8) or intralesional (n = 2) margins (5-year OS, radical or wide = 74%, marginal = 17%, intralesional = 0%, p = 0.044). The risk of local recurrence was significantly higher in the limb-salvage group compared to the amputation group (49% vs 0%, p = 0.011). OS and EFS were not significantly different between limb-salvage group and an amputation group (p = 0.188 and 0.912, respectively).ConclusionsWe believe non-metastatic, radiation-induced sarcoma of bone should be resected with the aim of achieving wide or radical margins. Although limb-salvage surgery was related to higher rates of local recurrence compared with those of the amputation group, OS and EFS were not different among two groups. Surgeons need to discuss the higher risk of local recurrence in limb-salvage surgery.     

High grade osteosarcoma of the extremities metastatic to the lung: Long-term results in 323 patients treated combining surgery and chemotherapy, 1985–2005

BackgroundApproximately one-third of patients with localized osteosarcoma at presentation relapse as well as about three-fourths of the patients with metastases at diagnosis, about 90% of relapses are lung metastases. The role of lung metastasectomy remains to be determined.Patientsand methods: Three hundred and twenty three patients, 88 with resectable lung metastases at diagnosis and 235 with localized disease at presentation who relapsed with lung metastases were treated.ResultsA total of 498 lung surgeries and 607 thoracotomies were performed. The 5 year overall survival was 37%. Final outcome was significantly related to presence or absence of metastasis, time of first relapse and presence of local recurrences. According to stage of the disease, the rate of a 5 year event-free survival (EFS) was 36% for patients with localized disease who later relapsed and 9% for patients with resectable lung metastases at presentation (p < 0.0001). However, there were no differences in EFS between patients who underwent two or three thoracotomies and patients who had four or five thoracotomies (7.5 vs 18.7%, p = 0.29).ConclusionsIn patients with recurrent resectable pulmonary metastases from high grade osteosarcoma treated with adjuvant or neoadjuvant chemotherapy, thoracotomy should always be considered regardless the number of previous lung relapses and the number of secondary pulmonary lesions.     

Risk factors in germ cell tumour patients with relapse or progressive disease after first-line chemotherapy: evaluation of a prognostic score for survival after high-dose chemotherapy

PurposeTo retrospectively re-evaluate a published prognostic score for response to salvage treatment in patients with germ-cell tumours relapsing or progressing after cisplatin-based first-line chemotherapy.Patients and methodsFrom a database of 257 germ cell tumour (GCT) patients treated with salvage high-dose chemotherapy (HDCT) we identified 176 patients (67%) with relapse or progression after first-line conventional-dose chemotherapy (CDCT). Patients were retrospectively grouped according to a published prognostic score defined by Fossa and colleagues [Fossa SD, Stenning SP, Gerl A, et al. Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumors. Br J Cancer 1999; 80:1392–9]. Overall survival (OS) and event free survival (EFS) after HDCT were retrospectively evaluated in each prognostic group.ResultsAfter a median follow-up of 9 years the OS probability for all 176 patients was 38% and the EFS probability was 35%. The respective survival probability at 5 years in 100/176 (57%) good prognosis patients and 76/176 (43%) poor prognosis patients were 47% versus 28% for OS (p < 0.001) and 41% versus 26% for EFS (p < 0.005). Whereas survival probabilities did not differ in good prognosis patients, OS and EFS in poor prognosis patients were substantially better in the current series of patients treated with HDCT compared to the ones reported by Fossa treated with CDCT.ConclusionThis retrospective analysis confirms the impact of prognostic factors on the results of salvage treatment in patients with GCT and suggests a clinical benefit for patients with poor prognosis features receiving a single course of HDCT.     

Rituximab Improves the Outcome of Patients With Grade 3 Follicular Lymphoma Receiving Anthracycline-Based Therapy

BackgroundThe combination of rituximab with chemotherapy has improved the outcome of patients with follicular lymphoma (FL). However, data on Grade 3 FL (FL3) and its subtypes are lacking. The aims of the study were to determine: (1) the clinical features and outcome of patients with FL3 treated with rituximab and anthracycline-based chemotherapy; and (2) the clinical significance of the 3 subtypes of FL3.Patients and MethodsEighty-seven patients with Grade 1/2 FL, 84 with FL3 including 46 FL3A, 17 FL3B, and 21 follicular large cleaved cell (FL3C), and 411 patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab and anthracycline-based chemotherapy, and a historical cohort of 167 patients with FL3 who received only anthracycline-based chemotherapy (FL3*) were included in this retrospective study.ResultsThe FL3 group had a significantly better overall survival (OS) and event-free survival (EFS) compared with those with FL3* or DLBCL. No significant differences in OS were found among the 3 subtypes of FL3. However, patients with FL3B had a shorter EFS than those with FL3A and FL3C. Moreover, patients with FL3B had an outcome similar to those with DLBCL, whereas patients with FL3A and 3C had significantly better outcomes than those with DLBCL. Less than 50% of the patients with FL3B and less than 20% of the patients with FL3A and 3C have relapsed, and relapses were uncommon after 5 years.ConclusionThe use of rituximab with anthracycline-based chemotherapy significantly improved the survival of patients with FL3 and should be considered the benchmark by which other therapies for FL3 are evaluated in the future.     

Treatment of Relapsed or Refractory Aggressive Non-Hodgkin Lymphoma with Two Ifosfamide-Based Regimens,IMVP and ICE

Abstract

We report the outcomes of 45 patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) treated with a combination of ifosfamide, carboplatinum and etoposide (ICE) and 28 patients treated with a combination of ifosfamide, methotrexate and etoposide (IMVP) during two 5-year periods. The response rate (RR) to ICE was 47%, 2-year overall survival (OS) 31% and 2-year event-free survival (EFS) 22%. These results were similar to those obtained with IMVP (RR 39%, 2-year OS 23%, 2-year EFS 13%; p=0.355 for RR, 0.275 for OS, 0.668 for EFS). Higher IPI scores and refractoriness to treatment were negative prognostic factors, immunophenotype (B vs. T) had no influence on prognosis. Changing from IMVP to ICE does not substantially improve the outcome of patients with relapsed or refractory aggressive NHL. Patients with relapsed/refractory aggressive B-NHL do not have a superior out-come in comparison to those with T-NHL if treated with chemotherapy alone.     

Adjuvant radiotherapy in stage IV diffuse large cell lymphoma improves outcome

The role of adjuvant radiotherapy to sites of nodal bulky disease in patients with aggressive diffuse large cell lymphoma (DLCL), and stage IV remain undefined. We began a prospective controlled clinical trial to evaluate impact in event free survival (EFS) and overall survival (OS) in a large cohort of patients with a longer follow-up. Between 1989 and 1995; 341 patients with aggressive DLCL and presence of nodal bulky disease (tumor mass > 10 cm) in pathological proven complete response after intensive chemotherapy were randomized to received either radiotherapy (involved fields, 40 Gy) or not. The 5-year EFS and OS in radiated patients were respectively: 82% (95% Confidence interval (CI): 70-89%) and 87% (95% 80-99%), that were statistically significant to control group: 55% (41-64%) (P < 0.001) and 66% (95% CI: 51-73%) (P < 0.01) respectively. Radiotherapy was well tolerated, acute toxicity was mild and until now late toxicity did not appear. The use of adjuvant radiotherapy improve EFS and OS and probably the possibility of cure in patients diffuse large cell lymphoma with worse prognostic factors. Thus, we felt that adjuvant radiotherapy will be considered as part of the initial treatment in this setting of patients.     

HER2 expression and efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients

No data are available on the role of HER2 overexpression in predicting the efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients. We retrospectively evaluated this role in patients enrolled in a phase III study comparing standard FEC21 (5-fluorouracil, epirubicin, and cyclophosphamide, administered every 3 weeks) vs dose-dense FEC14 (the same regimen repeated every 2 weeks). HER2 status was determined for 731 of 1214 patients. Statistical analyses were performed to test for interaction between treatment and HER2 status with respect to event-free survival (EFS) and overall survival (OS); EFS and OS were compared within each HER2 subgroup and within each treatment arm. Median follow-up was 6.7 years. Among FEC21-treated patients, both EFS (HR=2.07; 95% CI 1.27-3.38) and OS (HR=2.47; 95% CI 1.34-4.57) were significantly worse in HER2 + patients than in HER2 - patients. Among FEC14-treated patients, differences in either EFS (HR=1.21; 95% CI 0.65-2.24) or OS (HR=1.85; 95% CI 0.88-3.89) between HER2 + and HER2 - patients were not statistically significant. Interaction analysis suggested that the use of dose-dense FEC14 might remove the negative prognostic effect of HER2 overexpression on EFS and OS. Our data suggest a potential role of HER-2 overexpression in predicting the efficacy of dose-dense epirubicin-containing chemotherapy and the need to confirm this hypothesis in future prospective studies.     

Outcomes of Adolescent Patients with Acute Lymphoblastic Leukemia: Long-term Follow-up of 335 Patients

BackgroundAdolescents (aged 10-17 years) with acute lymphoblastic leukemia (ALL) represent a unique patient population, with a disproportionate survival disadvantage compared with younger patients. We aimed to determine the outcomes and prognostic factors of adolescent patients treated at our institution.Patients and MethodsBetween 2005 and 2017, 335 adolescents with ALL were enrolled; clinical characteristics and treatment outcomes were analyzed and compared between adolescents and younger children (1-9 years old, n = 704).ResultsAdolescents were more likely to have high-risk factors such as hyperleukocytosis, a T-cell immunophenotype, BCR-ABL1, and/or poor early treatment responses. Compared with younger children, adolescents had significantly worse 5-year event-free survival (EFS) (73.0% ± 2.5% vs. 82.6% ± 1.5%; P < .001) and overall survival (OS) (77.1% ± 2.3% vs. 87.7% ± 1.3%; P < .001). Furthermore, younger adolescents (10-14 years) tended to have better outcomes compared with those older than 15 years (5-year OS: 79.3% ± 2.5% vs. 68.4% ± 5.7%; P = .042), mainly because of the lower frequencies of toxicities. On multivariate analysis, white blood count ≥ 50 × 10⁹/L and extramedullary involvement at diagnosis were the most powerful prognostic factors for both OS and EFS.ConclusionThe outcomes among adolescent patients were not as good as that of younger children. Further studies are required to define optimal treatment strategies for adolescents, particularly those aged 15 to 17 years.     

Prognostic factors associated with survival in a large cohort of gastric cancer patients resected over a decade at a single Italian center: the Cremona experience

Background

Incidence of gastric cancer (GC) shows different distribution in Italy, with higher incidence in the north and center. We retrospectively analyzed the clinical data of patients resected at the Hospital of Cremona between January 2007 and December 2016. Available clinical variables were linked with survival to identify possible prognostic factors.

Materials and methods

Variables analyzed were age, sex, type of surgery, site, histology, invasion, nodal status, resection margins, grade, HER2 status, Helicobacter pylori infection (neo)adjuvant chemotherapy, adjuvant chemoradiotherapy, neutrophil-to-lymphocyte ratio, number of nodes removed and type of lymphadenectomy. Overall survival (OS) was estimated by the Kaplan–Meier method and differences between groups by the log-rank test. Data on OS were analyzed by Cox regression and the final model was obtained using the step-wise method.

Results

379 patients were considered, out of which 195 were operated from 2007 to 2011 and 184 from 2012 to 2016. Median follow-up was 25.5 months, median OS 31.3 months and time to recurrence 23.2 months. D2 resection rate increased from 36% (period 2007–2011) to 74% in 2012–2016 (p?=?0.01) with a higher mean number of nodes collected (20.98 for 2007–2011 and 23.53 for 2012–2016, p?=?0.040). Only 37% of patients received a postoperative treatment. At multivariate analysis, variables associated with OS were age (p?=?0.002), stage (p?<?0.001), resection margins status (p?<?0.001), adjuvant chemotherapy (p?<?0.010) and tumor location (cardia vs non-cardia) (p?=?0.029).

Conclusions

Our analysis shows that completeness of resection and lower stage are strong predictors of long-term survival in GC, providing the rationale for adjuvant and neoadjuvant approaches (chemotherapy, radiotherapy or combined). Cardial GC has worse prognosis compared to distal cancers.

Trial registration number

Service evaluation number 256, protocol 16821/17, date 05 June 2017.

     

High frequency of disease progression in pediatric spinal cord low-grade glioma (LGG): management strategies and results from the German LGG study group

BackgroundKnowledge on management of pediatric spinal cord low-grade glioma (LGG) is scarce.MethodsWe analyzed clinical datasets of 128 pediatric patients with spinal LGG followed within the prospective multicenter trials HIT-LGG 1996 (n = 36), SIOP-LGG 2004 (n = 56), and the subsequent LGG-Interim registry (n = 36).ResultsSpinal LGG, predominantly pilocytic astrocytomas (76%), harbored KIAA1549-BRAF fusion in 14/35 patients (40%) and FGFR1-TACC1 fusion in 3/26 patients (12%), as well as BRAFV600E mutation in 2/66 patients (3%). 10-year overall survival (OS) and event-free survival (EFS) was 93% ± 2% and 38% ± 5%, respectively. Disseminated disease (n = 16) was associated with inferior OS and EFS, while age ≥11 years and total resection were favorable factors for EFS. We observed 117 patients following total (n = 24) or subtotal/partial resection (n = 74), biopsy (n = 16), or radiologic diagnosis only (n = 3). Eleven patients were treated first with chemotherapy (n = 9) or irradiation (n = 2). Up to 20.8 years after diagnosis/initial intervention, 73/128 patients experienced one (n = 43) or up to six (n = 30) radiological/clinical disease progressions. Tumor resections were repeated in 36 patients (range, 2-6) and 47 patients required nonsurgical treatment (chemotherapy, n = 20; radiotherapy, n = 10; multiple treatment lines, n = 17). Long-term disease control for a median of 6.5 (range, 0.02-20) years was achieved in 73/77 patients following one (n = 57) or repeated (n = 16) resections, and in 35/47 patients after nonsurgical treatment.ConclusionsThe majority of patients experienced disease progression, even after years. Multiple interventions were required for more than a third, yet multimodal treatment enabled long-term disease control. Molecular testing may reveal therapeutic targets.     

Prognostic significance of the ratio of surgically resected to radiologically detected lung nodules in patients with metastatic osteosarcoma

The factors that affect the prognosis of patients’ metastatic osteosarcoma are still poorly understood. In this study, we investigated a new prognostic factor, the ratio of surgically resected to radiologically detected osteosarcoma lung nodules (SR/RD), which may have predictive value.Patients and methodsData from patients with metastatic osteosarcoma who underwent metastasectomy between January 2009 and December 2020, in a single center, were reviewed. The relationships between survival and the SR/RD ratio, timing of lung metastases, number of nodules, laterality, and presence of tumor necrosis at first metastasectomy were investigated.ResultsAmong the 125 metastatic osteosarcoma patients, 80 patients had an SR/RD ratio ≤1. The median duration of follow-up was 72 months, ranging from 6 to 118 months. The five-year overall survival (OS) and postmetastasectomy event-free survival (EFS) for all patients were 36.5% and 18.1%, respectively. The five-year OS of patients with a low SR/RD ratio was 49.6% and that of patients with a high SR/RD ratio was 11.8 (P = 0.001). The two-year postmetastasectomy EFS rates of the high and low ratio groups were 24.1% and 9.4%, respectively (P = 0.001). The SR/RD ratio, number of nodules, and tumor necrosis had significant effects on OS and postmetastasectomy EFS in univariate analysis. A Cox proportional hazard model demonstrated that tumor necrosis and an SR/RD ratio >1 were associated with OS (HR = 1.8 and 2.01) and postmetastasectomy EFS (HR = 1,69 and 1.97).ConclusionsA high SR/RD ratio of greater than 1 and poor tumor necrosis were significantly associated with poor survival among patients with metastatic osteosarcoma who had lung metastasectomy. The high SR/RD ratio may be a surrogate outcome for incomplete metastatic tumor resection.     

Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology

This study was designed to confirm the previously observed favorable survival rates and prognostic factors in young children with nonmetastatic medulloblastoma (MB) treated with postoperative chemotherapy alone. Patients who received a diagnosis during the period January 2001 through December 2005 and who were aged <4 years received 3 cycles of postoperative systemic multiagent chemotherapy and intraventricular methotrexate. In cases of complete remission, treatment was terminated after 2 additional cycles of chemotherapy. Otherwise, secondary surgery, radiotherapy, and consolidation chemotherapy were recommended. At a median follow-up of 4.5 years, the 5-year event-free survival (EFS) and overall survival (OS) rates (± standard error) for 45 patients (median age, 2.5 years) were 57% ± 8% and 80% ± 6%, respectively. Nineteen patients with desmoplastic/nodular MB variants had better 5-year EFS and OS rates (90% ± 7% and 100% ± 0%, respectively) than did 23 patients with classic MB (30% ± 11% and 68% ± 10%, respectively; P < .001 for EFS; P = .008 for OS). Five-year EFS and OS rates for 3 children with anaplastic MB were 33% ± 27%. Desmoplastic/nodular histology was an independent prognostic factor for EFS. Twenty-nine of 30 patients without postoperative residual tumor remained in continuous complete remission. Our results confirm that histology of MB variants is a strong prognostic factor in this age group. Sustained tumor control can be achieved by this chemotherapy regimen in young children with desmoplastic/nodular MB variants. For children with non-desmoplastic/nonnodular MB variants, for which predominantly local relapses lead to less favorable survival rates, local radiotherapy has been introduced after chemotherapy since 2006.