Five-year Progression-free Survival Rates Research Articles

Prognostic impact of immune inflammation biomarkers in predicting survival and radiosensitivity in patients with non-small-cell lung cancer treated with chemoradiotherapy.

The purpose of this retrospective study was to investigate the prognostic impact of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived NLR (dNLR) and systemic immune-inflammation index (SII) in predicting outcomes for patients with locally advanced non-small-cell lung cancer (NSCLC). The secondary endpoint was to evaluate the radiosensitivity in terms of response rate. Newly diagnosed locally advanced NSCLC patients were enrolled. Immune inflammation biomarkers were calculated from baseline blood samples. Patients were stratified in two groups based on optimal cut-off values for each biomarker. The associations between biomarkers and overall survival (OS), progression-free survival (PFS), local regional recurrence-free survival (LRRFS), and also response to radiotherapy were analysed. A total of 392 patients were included. Five-year OS, PFS and LRRFS rates were 14.6%, 12.1%, and 13.4% respectively. Optimal cut-off values for NLR, PLR, dNLR and SII were 3.07, 166, 2.02 and 817 respectively. Low NLR (HR 1.73, 95% CI 1.34-2.24, P < 0.001), low PLR (HR 1.37, 95% CI 1.06-1.76, P = 0.013), low dNLR (HR 1.66, 95% CI 1.29-2.13, P < 0.001) and low SII (HR 1.63, 95% CI 1.18-2.04, P < 0.001) were independent prognostic factors for OS. Low NLR, PLR, dNLR and SII were also significant prognostic factors for PFS and LRRFS. Low NLR, low dNLR and low SII groups had better radiosensitivity than compared with high NLR, high dNLR and high SII groups (P = 0.001, P = 0.001 and P = 0.012). NLR, PLR, dNLR and SII were independently associated with improved OS, PFS and LRRFS. Low NLR, dNLR and SII groups had better radiosensitivity. Immune inflammation biomarkers are promising prognostic predictors which can be obtained easily and inexpensively.

Five-year results of nivolumab for the treatment of non-small cell lung cancer in clinical practice of the N.N. Blokhin Russian Cancer Research Center

Introduction. Lung cancer remains the one of the most common and fatal cancers in the world. For a long time, chemotherapy was the only treatment option for metastatic lung cancer. Currently, immunotherapy became the one of the preferred options of treatment.The purpose of our work was to evaluate the long-term results of using the PD-1 inhibitor nivolumab in real-world settings.Materials and methods. 108 pretreated patients with metastatic NSCLC were included in this non-randomized, observational study. The median follow-up time was 54.5 months.Results. Median overall survival was 8.8 months (6-12, 95% CI). The five-year overall survival rate was 19.4%. Median progressionfree survival was 3.9 months (3-5, 95% CI). The five-year progression-free survival rate was 7.7%. Overall response rate (ORR) was 18%. In patients with ORR, the median overall survival was not achieved. Prolongation of immunotherapy after disease progression had a positive effect on the overall survival of patients. Clinically significant immuno-related adverse events developed in 21% of patients, but only 7.3% showed the development of adverse events grade 3-4 that required discontinuation of immunotherapy. A rare complication that we met was a case of encephalopathy, to which the patient achieved durable complete response despite discontinuation of immonotherapy.Conclusion. Received survival, efficacy and safety data may inform treatment decisions for patients with metastatic NSCLC in real world settings.

Comparison of surgical and oncologic outcomes in patients with clear cell ovarian carcinoma associated with and without endometriosis.

To compare clinical characteristics, surgical and oncologic outcomes of clear cell ovarian cancer among patients with cancer arising from endometriosis, cancer coexisting with endometriosis, and cancer without endometriosis. A retrospective chart review of patients diagnosed with clear cell ovarian cancer during January 1998-March 2013 was performed. All histopathology specimens were reviewed by a gynecologic pathologist and classified into one of the three following endometriosis status groups: arising group, coexisting group, or without group. The primary outcome was disease-specific survival (DSS). The secondary outcomes were progression-free survival, surgical morbidities, response rate, recurrence rate, and cancer-specific death. Finally, 249 patients were included. There were 82, 96, and 71 patients in the arising, coexisting, and without groups, respectively. Regarding baseline characteristics among groups, the without group was significantly older and had more advanced diseases. There was a significant difference in progression-free survival between the arising group and the without group (p = 0.003). Five-year progression-free survival rates were 62.8% in the arising group, 50.2% in the coexisting group, and 38.3% in the without group. DSS was not significantly different among groups. Multivariate analysis revealed ovarian surface invasion (HR = 2.76) and pelvic lymphadenectomy (HR = 0.39) to be independent prognostic factors for progression-free survival, whereas no remission after primary treatment (HR = 8.03) and pelvic lymphadenectomy (HR = 0.21) were prognostic factors for DSS. Intraoperative blood loss and residual tumor were significantly higher in the without group. Endometriosis status was found not to significantly influence surgical and oncologic outcomes in patients with clear cell ovarian cancer.

Prognostic impact of depth of response in Waldenström macroglobulinemia patients treated with fixed duration chemoimmunotherapy.

8049 Background: The treatment paradigm of Waldenström macroglobulinemia (WM) continues to evolve as new therapies expand our options for this indolent and incurable disease. While more profound responses are generally associated with longer treatment-free intervals, the impact of depth of response from fixed duration therapy in WM patients' survival needs further evaluation. In this international, multicenter cohort study, we report the prognostic impact of depth of response in WM. Methods: 319 WM patients treated with frontline fixed duration therapy [Dexamethasone/Rituximab/Cyclophosphamide (DRC), Bendamustine/Rituximab (BR), or Bortezomib/Dexamethasone/Rituximab (BDR)] were included. Response at the completion of therapy (6 months) was used in a landmark analysis for progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) (defined as time from 6 months post treatment response to event or censor). Response was defined by modified IWWM-6 criteria. Associations between clinical variables and outcomes were evaluated using Cox proportional-hazard models. Results: The median age at the time of treatment initiation was 64 years (range: 29-94), 59% were men, and risk category by International Prognostic Scoring System (IPSS)-WM was low (n=67, 23%), intermediate (n=83, 29%), and high-risk (n=141, 48%). Evaluable responses at 6 months from frontline therapy [DRC (n=105; 41%), BR (n=83; 32%), BDR (n=68; 27%)] were available in 256 patients and included in the landmark analysis. Median follow-up was 63 months (95% CI: 59-70). The rate of major response (PR or better) at 6 months was 74% for the entire cohort. Five-year PFS rates from completion of therapy for patients who attained major response vs. those who did not were 71% and 43%, respectively (p&lt;0.001). Five-year TTNT rates for patients who attained major response vs. not were 84% and 54%, respectively (p&lt;0.001). Five-year OS rates for patients who attained major response vs. not were 92% and 77%, respectively (p&lt;0.001). In multivariable analyses including other WM prognostic factors evaluated at initiation of frontline therapy, attaining a major response at 6 months was associated with superior PFS (HR 0.33, p&lt;0.001), TTNT (HR 0.23, p&lt;0.001), and OS (HR 0.31, p=0.001–Table). Conclusions: Achieving a major response at 6 months after frontline chemoimmunotherapy emerges as a significant prognostic factor for PFS, TTNT and OS in patients with WM.[Table: see text]

Different prognosis of stage IIIB cervical cancer patients with lower third of vaginal invasion and those without

ObjectivePrevious studies have evaluated the prognostic factors of patients with stage IIIB cervical cancer. However, there was only one study evaluating the relationship between LTI (lower third of vaginal invasion) and the prognosis of the patients with stage IIIB cervical cancer. Our research aimed to assess different therapeutic outcomes of the stage IIIB CCP (cervical cancer patients) with or without LTI. MethodsFrom December 2007 to December 2014, patients with FIGO (International Federation of Gynecology and Obstetrics, 2009) stage IIIB cervical cancer admitted and treated in Zhejiang Cancer Hospital were enrolled and evaluated in this retrospective research. Different clinicopathological variables and treatment outcomes were analyzed by using multivariate and univariate Cox regression models and chi-square or Fisher's exact test. ResultsThe number of enrolled patients was 622, among which 74 cases were with LTI and 548 without. The two- and five-year OS (overall survival) rates in non-LTI group were 79.9% and 58.9%, and the OS rates in LTI group were 68.9% and 38.8%, respectively (P = 0.001). The two- and five-year PFS (progression-free survival) rates in non-LTI group were 63.3% and 53.1%, and the PFS rates in LTI group were 45.9% and 37.0% respectively (P = 0.002). Multivariate Cox regression analysis indicated that histological type, total treatment time, hydronephrosis, and treatment protocol were factors significantly affecting the PFS rates in stage IIIB CCP, and OS rates were associated with histological type, hydronephrosis, treatment protocol, and LTI. ConclusionsOur study showed that stage IIIB CCP with LTI had worse prognosis than those without LTI.

Grading Soft Tissue Involvement in Nasopharyngeal Carcinoma Using Network and Survival Analyses: A Two-Center Retrospective Study.

Soft tissue involvement (STI) indicates poor prognosis in nasopharyngeal carcinoma (NPC). However, only a few studies have systematically assessed this extension using network analysis. To investigate the prognostic value of STI and to propose an improved STI grading system for NPC therapy. Retrospective study. A total of 1225 consecutive patients with pathologically confirmed NPC treated with intensive-modulated radiotherapy from January 2010 to March 2014 were enrolled from two centers. T1- and T2-weighted imaging and enhanced T1-weighted imaging with fast spin echo sequence at 1.5 or 3.0T. The levator veli palatini and tensor veli palatini involvement were graded "mild," prevertebral muscle involvement, "moderate," medial pterygoid, lateral pterygoid, and the infratemporal fossa involvement, "severe" STI. The above STI sites were evaluated separately by three radiologists using MRI images and graded using network analysis. Overall survival (OS) and progression-free survival (PFS) were assessed. Kaplan-Meier method, Cox's proportional hazards model, and concordance index (C-index) were used. Five-year OS and PFS rates between mild and moderate groups (90.5% vs. 81.7%, P < 0.05 and 82.9% vs. 72.5%, P < 0.05, respectively) and between moderate and severe groups (81.7% vs. 70.4%, P < 0.05 and 72.5% vs. 61.2%, P < 0.05, respectively) revealed significant differences. The C-index of the nomogram with STI grading was higher compared with current T-classification (OS 0.641 vs. 0.604, P < 0.05 and PFS 0.605 vs. 0.581, P < 0.05, respectively). Significant OS differences were observed between patients with severe STI who underwent induction chemotherapy (IC) and those who did not (84.5% vs. 70.7%, P < 0.05). STI grading was an independent prognostic factor for OS and PFS in NPC patients and it may be help to improve the accuracy in predicting survival outcomes. Patients with severe STI might benefit from IC to improve OS. 4 TECHNICAL EFFICACY: Stage 2.

Clinical Impact of Pelvic Lymph Node Status in Locally Advanced Cervical Cancer Patients Treated by Concurrent Chemoradiation Therapy.

Objective:To explore the treatment outcomes of locally advanced cervical cancer (LACC) patients with pelvic lymph node enlargement (PLNE) or stage IIIC1 when compared with no PLNE and unknown PLN status (UNK). Materials and Methods:Retrospective cohort study was designed by matching with the ratio of 1:4:4 for patients with PLNE, no PLNE and UNK between 2003 and 2017. The main factor which was used to match was clinical staging. Results:All 360 LACC patients who treated as concurrent chemoradiation therapy (CCRT) were composed of 40 with PLNE, 160 with no PLNE and 160 with UNK. The majority of tumor histology (78.9%) was squamous cell carcinoma and 51.1% were diagnosed in stage IIB. Five-year progression free survival rates of patients with PLNE, no PLNE and UNK were 42.7%, 64.5% and 59.0%, respectively (P = 0.191), and corresponding with 5-year overall survival rates of 57.0%, 66.0% and 61.9% (P = 0.608). Patients with PLNE had local recurrence (LR) at 22.5%, compared with no PLNE at 11.3% and UNK at 11.9%. The most common site of LR for patients with PLNE was PLN with odds ratio of 19.7 when using no PLNE as reference (P < 0.001). There was no statistically significant difference between distant metastasis rates in PLN statuses of patients with PLNE, no PLNE and UNK at 20.6%, 30.0% and 26.3%, respectively. Conclusions:LACC patients with PLNE had a trend of poorer survival rates than patients with no PLNE, while treatment outcomes of patients with UNK were not inferior to no PLNE.

Clinical features & treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma.

Background & objectives:Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a common marginal zone lymphoma. The stomach is the relatively common origin of the MALT lymphoma, now termed as extranodal marginal zone B-cell lymphoma. Gastric MALT lymphoma has good prognosis due to clinical response to treatment and favourable overall survival. In this study, clinical characteristics and treatment of patients of early gastric MALT lymphoma were retrospectively analysed.Methods:Seventy patients with stages I–II MALT-lymphoma treated from April 2003 to August 2015 were included. The most common symptoms were abdominal discomfort, nausea, vomiting and other digestive symptoms. Helicobacter pylori eradication was done in patients with proven H. pylori infection. Patients in whom H. pylori eradication therapy was not effective, alternative treatments options including chemotherapy, radiotherapy and surgery, were given.Results:Fifty two patients with H. pylori infection underwent anti-H. pylori therapy, the total effective rate of anti-H. pylori treatment was 92.3 per cent (48/52). Thirty two patients were given anti-tumour treatment, including chemotherapy, radiotherapy and surgery. The total effective rate was 90.6 per cent (29/32). The five-year overall survival rate and five-year progression-free survival rate were 93.4 and 84.2 per cent, respectively.Interpretation & conclusions:For patients with early gastric MALT lymphoma, anti-H. pylori treatment may be effective. Patients with poor results of anti-H. pylori treatment need to be treated with anti-tumour therapy.

AS1-KL-1 DEVELOPMENT OF HIGH-DOSE CHEMOTHERAPY INCLUDING THIOTEPA COMBINED WITH AUTOLOGOUS PERIPHERAL BLOOD STEM CELL RESCUE

Thiotepa is a classic alkylating agent that was launched in 1958 in Japan. We have consistently developed thiotepa-containing HDC since 1992, inspired by the fact that thiotepa was used as an alternative to melphalan as a high-dose chemotherapy (HDC) drug for neuroblastoma in the United States. Thiotepa is considered to be a drug suitable for brain tumor treatment because of its good BBB permeability, equal concentration in cerebrospinal fluid and blood, and the characteristics of alkylating agents that enhance the effect by log ratio of dose. Melphalan, which is also an alkylating agent as a central agent of HDC, has a strong antitumor effect, so we planned to use both at the maximum tolerated dose for each. Therefore, in order to reduce toxicity, it was decided to divide it into two doses at weekly intervals and to administer thiotepa for 24 hours in order to prevent hepatic sinus obstruction syndrome (SOS). Since 1993, a dose determination study was conducted, and the doses of thiotepa and melphalan were determined to be 800 mg/m2 and 280 mg/m2, respectively. Autologous peripheral blood stem cell transplantation using this regimen was performed as a consolidation therapy for metastatic pediatric medulloblastoma in 28 and 15 patients, respectively, in 2 series. Five-year progression-free survival rates of 82.1 ± 7.2% and 92.9 ± 6.9% were obtained. After that, the supply was stopped in 2009. This time, a domestic study was conducted with the dose of melphalan reduced to 210 mg/m2, and this year, a new indication (pretreatment for autologous hematopoietic stem cell transplantation in childhood malignant solid tumors) was acquired and launched. By this dose reduction, reduced gastrointestinal toxicity such as mucosal damage is expected. The JCCG clinical trials incorporating HDC will be conducted in medulloblastoma, ATRT, and refractory germ cell tumors.

Lymphocyte-monocyte ratio predicts uterine sarcoma aggressiveness

Purpose of Investigation: The aim of the current study is to assess the prognostic value of the lymphocyte-monocyte ratio (LMR) in patients with uterine sarcoma. Materials and Methods: The authors examined the LMR as a prognostic variable in a cohort of 66 patients with uterine sarcoma who underwent surgical resection. Patients were categorized into two groups based on the LMR using cut-off values determined by receiver operating characteristic curve (ROC) analysis. They assessed the effect of the LMR on progression-free survival (PFS) and validated the LMR as independent predictor of survival. Results: Using data from the whole cohort, the optimized LMR cut-off value selected using the ROC curve was 5.86 for PFS. The LMR-low and LMR-high groups included 45 (68.2%) and 21 (31.8%) patients, respectively. The five-year PFS rates in the LMR-low and LMR-high groups were 69.0% and 94.4%, respectively (p= 0.024). Via multivariate analysis, the authors identified FIGO stage, residual tumor after surgery, and LMR as the most valuable prognostic factors affecting PFS (p = 0.039, p = 0.018, and p = 0.043, respectively). Conclusion: The LMR is an independent prognostic factor affecting the PFS of patients with uterine sarcoma.

Long-term effect of risk-adaptive therapy for early stage extranodal NK/T cell lymphoma

Objective: This study aimed to evaluate the role of extended involved-field intensity modulated radiation therapy (IMRT) for patients with early stage extranodal nasal-type NK/T-cell lymphoma (NKTCL) in a single center, and to explore the long-term effect of risk-adaptive therapy. Methods: Among 238 patients with early stage NKTCL, there were 191 in high-risk group [any risk factor of age > 60, elevated serum lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group (ECOG) score≥2, primary tumor invasion, or Ann Arbor stage Ⅱ] and 47 in low-risk group (no risk factor). A total of 204 patients received radiotherapy combined with chemotherapy, 15 received radiotherapy alone and 19 received chemotherapy alone. One-hundred and eighty-six patients had radiotherapy at a dose ≥50 Gy and 159 patients received chemotherapy with asparaginase-based regimen. Results: The 5-year overall survival (OS) rate and progression- free survival (PFS)rate of all patients were 66.2% and 57.5%. Five-year OS and PFS rates in low-risk group were 91.8% and 88.0%, while 59.3% and 49.3% in high-risk group. The survival of patients in low-risk group were better than those in high-risk group (both P<0.001). The five-year OS rate in combined therapy group, radiotherapy group and chemotherapy group were 71.7%, 52.3% and 20.7%, respectively (P<0.001). The five-year PFS rate were 63.5%, 23.3% and 24.1%, respectively (P<0.001). Among 219 patients receiving radiotherapy, the 5-year OS and PFS rate of patients with primary site radiotherapy dose ≥ 50 Gy were 72.6% and 66.1%, higher than those of patients with a dose <50 Gy (57.3% and 30.9%, respectively; P=0.031, P<0.001). In the high-risk group, the 5-year OS and PFS rate of the patients who received radiotherapy combined with more than 4 cycles of chemotherapy were 66.5% and 62.6%, higher than those of patients received less than 4 cycles of chemotherapy (56.7% and 46.4%, P=0.045 and 0.020, respectively). Cox multivariate analysis showed that ECOG score (HR=2.208, P=0.001), primary site (HR=4.887, P<0.001), primary tumor invasion (HR=3.265, P=0.001) and radiation dose (HR=1.895, P=0.011) were independent factors of OS in early NKTCL patients. Conclusion: Extended-involved field IMRT with radiation dose more than 50 Gy was the main treatment for patients with early stage NKTCL. Radiotherapy combined with adequate cycle chemotherapy significantly improved prognosis of high-risk patients.

Long-term efficacy of imatinib mesylate in patients with advanced Tenosynovial Giant Cell Tumor

Tenosynovial giant cell tumors (TGCT), are rare colony stimulating factor-1(CSF-1)-driven proliferative disorders affecting joints. Diffuse-type TGCT often causes significant morbidity due to local recurrences necessitating multiple surgeries. Imatinib mesylate (IM) blocks the CSF-1 receptor. This study investigated the long term effects of IM in TGCT. We conducted an international multi-institutional retrospective study to assess the activity of IM: data was collected anonymously from individual patients with locally advanced, recurrent or metastatic TGCT. Sixty-two patients from 12 institutions across Europe, Australia and the United States were identified. Four patients with metastatic TGCT progressed rapidly on IM and were excluded for further analyses. Seventeen of 58 evaluable patients achieved complete response (CR) or partial response (PR). One- and five-year progression-free survival rates were 71% and 48%, respectively. Thirty-eight (66%) patients discontinued IM after a median of 7 (range 1–80) months. Reported adverse events in 45 (78%) patients were among other edema (48%) and fatigue (50%), mostly grade 1–2 (89%). Five patients experienced grade 3–4 toxicities. This study confirms, with additional follow-up, the efficacy of IM in TGCT. In responding cases we confirmed prolonged IM activity on TGCT symptoms even after discontinuation, but with high rates of treatment interruption and additional treatments.

Favorable outcomes with de-escalated radiation therapy for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma

AbstractRadiation fields for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have shrunk over time; involved-site radiation therapy (ISRT) has replaced extended-field radiation therapy (EFRT) and involved-field radiation therapy (IFRT), but this has not been validated. The role of systemic therapy is unclear. We reviewed 71 stage I/II NLPHL patients and assessed progression-free survival (PFS), overall survival (OS), locoregional disease-free survival, and distant disease-free survival (DDFS). Median patient age was 39 years, and 61% had stage II disease. Thirty-six (51%) received radiation therapy (RT) only, 6 (8%) received systemic therapy only, and 29 (41%) received both. More patients receiving combined therapy had B symptoms (P = .035) and stage II disease (P = .001). In the RT-only group, 9 (25%) received EFRT, 13 (36%) received IFRT, and 14 (39%) received ISRT; in the combined-modality group, 3 (10%) received EFRT, 7 (24%) received IFRT, and 19 (66%) received ISRT. After a median follow-up of 6.2 years, 15 patients relapsed (13 distant, 2 locoregional). Five-year PFS and OS rates were 86% and 96% and did not differ by treatment. In the RT-only group, follow-up was shorter in the ISRT cohort (2.6 years vs 17.9 years [EFRT] and 8.5 years [IFRT], P < .01), but 5-year PFS did not differ by field size (P = .20). Locoregional control rates were 100% for the RT-only and combined groups, and corresponding 5-year DDFS rates were 93% and 95% (P = .95). Eight patients (11%) experienced a second malignancy (1 within RT field). Six patients died (1 from lymphoma). Use of limited ISRT fields does not appear to increase the risk of locoregional relapse, even when RT is given as single-modality therapy.

Survival outcomes after adjuvant radiotherapy for aggressive fibromatosis depend on time frame and nuclear β-catenin.

PurposeTo identify prognostic factors influencing progression-free survival (PFS) of aggressive fibromatosis (AF) after postoperative radiotherapy (PORT) and assess correlations between immunohistochemistry (IHC) features of β-catenin/smooth muscle actin (SMA) and PFS.Materials and MethodsRecords of 37 patients with AF treated by PORT from 1984 to 2015 were retrospectively reviewed. Fifteen patients underwent wide excision for AF and 22 patients received debulking operation. The median total dose of PORT was 59.4 Gy. IHC staining results of β-catenin and SMA were available for 11 and 12 patients, respectively.ResultsThe median follow-up duration was 105.9 months. Five-year PFS rate was 70.9%. Tumor size or margin status was not related to PFS in univariate analysis (p = 0.197 and p = 0.716, respectively). Multivariate analysis showed that increased interval from surgery to PORT (>5.7 weeks) was a marginal risk factor for PFS (p = 0.054). Administration of PORT at the initial diagnosis resulted in significantly improved PFS compared to deferring PORT after recurrence (p = 0.045). Patient with both risk factors of deferring PORT after recurrence and interval from surgery to PORT >5.7 weeks had significantly lower 5-year PFS than patients without risk factor (34.1% vs. 100.0%; p = 0.012). Nuclear β-catenin intensity tended to inversely correlate with 5-year PFS, although it did not reach statistical significance (62.5% at low vs. 100.0% at high; p = 0.260). SMA intensity was not related to PFS (p = 0.700).ConclusionPORT should be performed immediately after surgery irrespective of margin status or tumor size especially in recurrent case. Nuclear β-catenin staining intensity of IHC might correlate with local recurrence.

Investigating the potential benefit of second biopsy of residual mass in pediatric mature B cell non-Hodgkin lymphoma

Objectives: To assess the impact of second-look biopsy of residual mass during or after chemotherapy in pediatric mature B-cell NHL.Methods: Patients with mature B-cell non-Hodgkin lymphoma (NHL) who were suspicious of radiological residual mass at mid or end of treatment and subjected to second biopsy were treated at our center between January 2001 and December 2015. Their clinical characteristics, imaging findings, pathological changes, management, and prognosis were reviewed retrospectively.Results: A total of 31 children were included (13 boys and 18 girls, median age at diagnosis 6.1 years). The median time from diagnosis to second biopsy was 3.15 months (range 2.3–18 months). Biopsy confirmed the presence of viable tumor in eight patients. The specificity and positive predictive value of conventional imaging in detecting residual detectable by biopsy were at 9 and 28.6%, while sensitivity and negative predictive value of this approach were both 100%. Three of the histologic positive patients experienced progressive disease or relapse while the others achieved complete remission (CR) and 21 patients achieved long-time CR at median follow-up of 3.2 years. The median progression-free survival (PFS) time of all 31 was 28 months and 5-year PFS rate was 90.0%. Five-year PFS rate of negative-biopsy and positive-biopsy group were 100 and 62.5%, respectively (p = 0.002).Conclusion: Conventional imaging has very high sensitivity but very low specificity for the accurate determination of residual disease in pediatric NHL. Second-look biopsy is necessary to differentiate viable tumor from necrosis or fibrosis and is solid evidence-based foundation of subsequent treatment.

A comparison of treatment outcome between fiducial-based and bone-based image guided radiotherapy in prostate cancer patients

Background and purposeTo compare the clinical outcome in prostate cancer patients treated with radiotherapy using two forms of image guidance: bone-based (BB) or fiducial-based (FB).Material and methodsThis retrospective study consisted of 180 patients treated with kV-kV image-guided radiotherapy (IGRT) between the years 2008 and 2011. A total of 89 patients were aligned to pelvic bone (Group BB) and 91 patients to the fiducial implanted into prostate for image guidance (Group FB). Patients were treated to a total dose of 76 Gy in 38 fractions. The Cox Regression Model was used to evaluate the influence of clinical and treatment-related parameters on overall survival, biochemical progression and progression-free survival. Acute and late toxicity were evaluated based on the RTOG/EORTC criteria. Sexual function was assessed with QLQ PR-25 (EORTC QLQ forms). An assessment of the differences in patient daily set-up from the time of simulation was performed.ResultsThe incidence of acute G2/G3 genitourinary (GU) and gastrointestinal (GI) toxicity was similar between groups. In the BB group, 34 patients had G2 and 5 had G3 GU acute toxicity - compared to 40 patients with G2 and 2 with G3 in the FB group. G2 and G3 GI acute toxicity was observed respectively in 24 patients and in 1 patient in the BB group compared to 18 patients with G2 and 1 patient with G3 toxicity in the FB group. The five-year incidence of late ≥G2 GU toxicity was 12% in both groups (p = 0.98) and ≥ G2 GI toxicity 19% (BB) vs 15% (FB, p = 0.55), respectively. The five-year progression-free survival rate was 87% in BB and 81% in the FB Group (p = 0.15). The 5-year Overall Survival rate (OS) was 80% (BB) vs 91% % (FB, p = 0.20), but the difference was most pronounced in the intermediate-risk group: 5-year OS of 93% (FB) and 75% (BB), respectively (p = 0.06). No significant changes were observed in sexual or erectile functioning as compared to that specified at the beginning of radiotherapy and between the FB and BB Groups.ConclusionWhen comparing bone-based to fiducial-based techniques, no differences in clinical outcomes or late toxicity were seen in this population. However, intermediate risk prostate cancer patients are those who might benefit most from implementation of fiducial-based IGRT.

Treatment outcomes of proton or carbon ion therapy for skull base chordoma: a retrospective study

BackgroundThe usefulness of particle therapy for skull base chordoma has not been established. The aim of this retrospective study was to analyse the treatment outcomes of proton therapy (PT) and carbon ion therapy (CIT) in patients with skull base chordoma at a single institution.MethodsAll patients who underwent PT or CIT with curative intent between 2003 and 2014 at Hyogo Ion Beam Medical Center were included in this study. Twenty-four patients were enrolled. Eleven (46%) received PT and 13 (54%) received CIT. Overall survival (OS), progression-free survival (PFS) and local control (LC) were calculated using the Kaplan–Meier method. Late toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0.ResultsThe median follow-up was 71.5 months (range, 14–175 months). The five-year LC, PFS and OS rates were 85, 81, and 86%, respectively. The LC (P = 0.048), PFS (P = 0.028) and OS (P = 0.012) were significantly improved in patients who had undergone surgery before particle therapy. No significant differences were observed in the LC rate and the incidence of grade 2 or higher late toxicities between patients who received PT and CIT.ConclusionsBoth PT and CIT appear to be effective and safe treatments and show potential to become the standard treatments for skull base chordoma. To increase the local control, surgery before particle therapy is preferable.

Loss of BAP1 expression in metastatic tumor tissue is an event of poor prognosis in patients with metastatic clear cell renal cell carcinoma

PurposeTo evaluate the prognostic impact of the protein expression of both PBRM1 and BAP1 in metastatic tissue of patients with metastatic clear cell renal cell carcinoma (ccRCC). Patients and methodsIn all 124 consecutive cases of metastatic ccRCC, who underwent metastasectomy or biopsy of metastatic tumor tissue between 2007 and 2016 were selected from the medical records of our institution. Additionally, 38 paired cases with tissue from the primary tumor involving radical or partial nephrectomy for ccRCC were also selected. All cases were reviewed for uniform reclassification and the most representative tumor areas were selected for the construction of a tissue microarray. ResultsPBRM1 nuclear staining of the 124-immunostained metastases of ccRCC specimens showed that 98 (79.0%) had negative expression and 26 (21.0%) positive expression of PBRM1. Regarding BAP1 expression, we observed that 77 (62.1%) specimens were negative and 47 (37.9%) showed positive nuclear staining. When we compared the expression of both markers on primary tumor and tumor metastasis, we found disagreement in half of the cases. Five-year overall survival rates in patients with positive expression and negative expression of BAP1 were 53.2% and 35.1%, respectively (P = 0.004). Five-year progression-free survival rates in patients with positive expression and negative expression of BAP1 were 14.9% and 3.9%, respectively (P = 0.003). Conversely, PBRM1 expression did not significantly influence either overall survival or progression-free survival rates. In multivariate analysis, negative expression of BAP1 tumors also presented higher risks of death (hazard ratio (HR) = 1.913, P = 0.041) and disease progression (HR = 1.656, P = 0.021). ConclusionThe use of prognostic biomarkers identified in the primary tumor tissue might be not reliable in the metastatic disease scenario. Patients with metastatic ccRCC that present loss of BAP1 expression in metastatic tissue demonstrated poor survival rates and represent a relevant risk group for tumor recurrence and death.

The predictive value and the correlation of peripheral absolute monocyte count, tumor-associated macrophage and microvessel density in patients with colon cancer.

The tumor microenvironment plays a pivotal role in cancer progression. The purpose of the present study was designed to evaluate the predictive value of peripheral absolute monocyte count, tumor-associated macrophage, microvessel density, and to clarify the correlation between them in patients with colon cancer.A series of 216 patients with colon cancer were enrolled in this study. The peripheral absolute monocyte count was obtained from preoperative routine blood test. Tumor-associated macrophage and microvessel density were assessed on tissue microarray by immunohistochemistry.The one, three, five-year overall survival rate for the low absolute monocyte count group was 98.4%, 91.1%, 87.1%, respectively; and for the high absolute monocyte count group was 94.6%, 83.7%, 77.2%, respectively (P = .046). The one, three, five-year progression-free survival rate for the low absolute monocyte count group was 94.4%, 87.1%, 85.5%, respectively; and for the high absolute monocyte count group was 90.2%, 75.0%, 73.9%, respectively (P = .024). Univariate and multivariate analysis showed that there was a strong association between peripheral monocyte count and clinical outcome. The correlation between peripheral absolute monocyte count, tumor-associated macrophage, and microvessel density were not observed.The peripheral absolute monocyte count was an independent prognostic factor for overall survival and progression-free survival in colon cancer. The high absolute monocyte count was significantly associated with poor outcome.

Predictors of distant relapse in patients with FIGO stage IIB-IVA cervical cancer treated with definitive radiotherapy.

To investigate the predictors of distant relapse in International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IVA cervical cancer patients treated with definitive radiotherapy (RT). The clinical data of 219 patients with FIGO stage IIB-IVA cervical cancer treated with definitive RT between January 1997 and December 2011 were retrospectively reviewed. The cumulative distant relapse, progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards regression model was used to investigate the predictors of distant relapse in patients. Following treatment with definitive RT, 61 of the 219 (27.9%) patients developed distant relapse with median PFS and OS rates of 9.9 and 32.8 months, and estimated five-year PFS and OS rates of 4.9% and 21.3%, respectively. Multivariate analysis revealed that pelvic node metastasis, pretreatment leukocytosis and pretreatment neutrophilia were significant predictors of distant relapse. The risk of developing distant relapse was found to be associated with the number of predictors that the patients displayed: the estimated five-year distant relapse rates of the patients with no predictors, one predictor and two predictors were 20.3%, 35.5% and 88.9%, respectively. Roughly 28% of patients with FIGO stage IIB-IVA cervical cancer developed distant relapse after definitive RT. Pelvic lymph node metastasis and pretreatment leukocytosis/neutrophilia are independent predictors of distant relapse.