Significant Negative Prognosticator Research Articles

Prognostic 18F-flotufolastat PET parameters for outcome assessment of 177Lu-labeled PSMA-targeted radioligand therapy in metastatic castration-resistant prostate cancer.

This retrospective analysis evaluates baseline 18F-flotufolastat positron emission tomography (PET) parameters as prognostic parameters for treatment response and outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment with [177Lu]Lu-PSMA-I&T. A total of 188 mCRPC patients with baseline 18F-flotufolastat PET scans were included. Tumor lesions were semiautomatically delineated, with imaging parameters including volume-based and standardized uptake value (SUV)-based metrics. Outcome measures included prostate-specific antigen (PSA) response, PSA-progression-free survival (PSA-PFS), and overall survival (OS). Univariate and multivariate regression analyses assessed the impact of baseline imaging and pretherapeutic clinical parameters on outcome. Event time distributions were estimated with the Kaplan-Meier method, and groups were compared with log-rank tests. Significant prognostic parameters for PSA response and PSA-PFS included log-transformed whole-body SUVmax (odds ratio (OR), 3.26, 95% confidence interval (CI), 2.01-5.55 and hazard ratio (HR), 0.51, 95% CI, 0.4-0.66; both p < 0.001) and prior chemotherapy (OR 0.3, 95% CI, 0.12-0.72 and HR 1.64, 95% CI, 1.07-2.58; p = 0.008 and p = 0.028, respectively). For OS, significant prognosticators were the following log-transformed parameters: number of lesions (HR 1.38, 95% CI, 1.24-1.53; p < 0.001), TTV (HR 1.27, 95% CI, 1.18-1.37; p < 0.001), and ITLV (HR 1.24, 95% CI, 1.16-1.33; p < 0.001), with log-transformed TTV (HR 1.15, 95% CI, 1.04-1.27; p = 0.008) remaining significant in multivariate analysis. At baseline, SUV-based 18F-flotufolastat PET metrics (e.g., whole-body SUVmax) serve as significant positive prognosticators for short-term outcomes (PSA response and PSA-PFS). In contrast, volume-based metrics (e.g., TTV) are significant negative prognosticators for long-term outcome (OS), in mCRPC patients treated with [177Lu]Lu-PSMA-I&T.

Are dynamic or fixed FDG‐PET measures of disease of greater prognostic value in patients with relapsed/refractory diffuse large B‐cell lymphoma undergoing autologous haematopoietic stem cell transplantation?

Positron emission tomography (PET) response assessment using the Deauville score has prognostic utility in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem-cell transplantation (ASCT). Improved predictive methods are required to identify patients with poor outcomes who may be better considered for other salvage options. We investigated the prognostic value of mean tumour volume (MTV) and maximum standardised uptake value (SUVmax) at pre-salvage and pre-ASCT time-points, and the quantitative changes between scans (∆MTV and ∆SUVmax). One hundred and twenty-five patients with R/R DLBCL underwent salvage immunochemotherapy and ASCT: 80 patients had pre-salvage PET and 90 had pre-ASCT PET available. With a median follow-up of 5.6 years, 5-year progression-free survival (PFS) and overall survival (OS) were 52% and 65%, respectively. For patients with PET-positive residual disease after salvage therapy, pre-ASCT MTV was a significant negative prognosticator for PFS (HR1.19 per 100 ml, p< 0.001) and OS (HR1.78 per 100 ml, p< 0.001). Similarly, pre-ASCT SUVmax was negatively associated with PFS (HR1.08, p< 0.001) and OS (HR1.08, p< 0.001). Notably, pre-salvage MTV and SUVmax and ∆MTV and ∆SUVmax were not associated with PFS or OS. In conclusion, pre-ASCT MTV and SUVmax appear to be of greater predictive value than the degree of response. Potential application may exist for PET-directed management of R/R DLBCL patients.

The impact of the extent of the bone involvement on overall survival and toxicity in mCRPC patients receiving [177Lu]Lu-PSMA-617: a WARMTH multicentre study.

Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement. The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [177Lu]Lu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6-20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18months (less than 6 lesions), 13months (6-20 lesions), 11months (more than 20 lesions) and 8months (diffuse involvement), respectively (p < 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6-20 lesions (OS: 16 vs. 12months; p = 0.038) as well as diffuse involvement (OS: 11 vs. 7months; p = 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with <6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases: p < 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia. The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.

Association of planning target volume with disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition.

e20557 Background: The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Methods: Prospective data of thirty-nine consecutive patients with inoperable stage III NSCLC who completed CRT with sequential durvalumab (72%, 28 patients) or concurrent and sequential nivolumab (28%, 11 patients) were analyzed. Different cut offs for PTV as well as PTV as a continuous variable were evaluated for association with progression-free survival (PFS) and extracranial metastasis-free survival (eMFS). Results: All patients were treated with conventionally fractionated TRT to a total dose of at least 60 Gy (range: 60-63.6Gy), 97% (27 patients) received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 23.2 (range: 6.0-42.6) months; median overall survival (OS) and eMFS were not reached. Median Progression-free survival (PFS) was 22.8 (95% CI: 10.3-35.2) months. Age (65 years), gender and UICC stage had no significant impact on PFS. There was no significant difference between durvalumab and nivolumab patients. Patients with PTV ≥ 900ccm had a significantly shorter PFS (11.77 vs 26.3 months, p = 0.049) and eMFS (11.7 months vs not reached, p = 0.019). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (TNM 8th Ed.) achieved a dismal median PFS of only 3.6 months (vs. 26.3 months p &lt; 0.001). PTV as a continuous variable showed a trend for association with PFS (p = 0.064) and was a significant negative prognosticator for eMFS (p = 0.030; HR: 4.065; 95%CI: 1.148-14.397). Conclusions: PTV has a significant impact on the PFS and eMFS after CRT combined with concurrent and/or sequential CPI in inoperable stage III NSCLC. Patients with PTV ≥ 900ccm had a significantly shorter PFS and eMFS.

Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer.

Simple SummaryGallbladder cancer (GBC) is an aggressive malignancy with poor prognosis. Currently, therapeutic options are mostly limited to palliative chemotherapy. Considering the advances of immunotherapy, we assessed the expression of the programmed cell death ligand-1 (PD-L1) as the most widely used predictive marker for immunotherapy response in a large Western-world GBC cohort. Additionally, we quantified the expression of the T-cell immunoreceptor with Ig and ITIM domains TIGIT/CD155 axis as an emerging immune checkpoint. Our results indicate that PD-L1 is heterogeneously expressed in Western-world GBC and associated with distinct histomorphological tumor subtypes and increased immune cell densities. We show that a high tumoral PD-L1 expression is a significant negative prognosticator. In a subset of patients, we identified expression of TIGIT in scattered immune cells, which correlated with tumoral expression of its ligand CD155. Our results suggest a subset of GBC patients to be candidates for immunotherapy via (combined) PD-L1 and TIGIT/CD155 inhibition.Inhibition of the programmed cell death protein-1/ligand-1 (PD-1/PD-L1) axis has opened a new era in the treatment of solid cancers. However, there is no data on the expression and relevance of PD-L1 in Western gallbladder cancer (GBC). We assessed PD-L1 immunohistochemically in 131 GBC patients as Tumor Proportion Score (TPS), Immune Cell Score (IC) and Combined Positivity Score (CPS). Tumor cells expressed PD-L1 in a subset of 14.7% GBC patients at a TPS cut-off of 1%. Higher PD-L1 levels above 10% and 25% TPS were reached in 4.7% and 3.1% of GBC cases, respectively. At a 10% cut-off, TPS was associated with distinct histomorphological subtypes and correlated with poor tumor differentiation. Survival analysis revealed a TPS above 10% to be a highly significant and independent negative prognosticator in GBC. PD-L1 expression was associated with increased CD4+, CD8+ and PD-1+ immune cell densities. In 14.8% of the cases, scattered immune cells expressed T-cell immunoreceptor with Ig and ITIM domains (TIGIT), which was correlated to tumoral expression of its ligand CD155. We here show that a high PD-L1 expression confers a negative prognostic value in Western-world GBC and highlight the TIGIT/CD155 immune checkpoint as a potential new target for GBC immunotherapy.

Detection of bone metastases in uterine cancer: How common are they and should PET/CT be the standard for diagnosis?

ObjectivesOsseous metastases (OM) in endometrial cancer (EMCA) are thought to be rare. This study aimed to address the gap in present knowledge by defining the rate of OM in endometrial cancer (EMCA) as stratified by histology and ascertaining the best diagnostic modality for detection. Methods435 consecutive cases of EMCA evaluated in tertiary care setting were reviewed. Clinico-pathologic data were abstracted and analyzed. Results18/403 patients were found to have OM (4.6%). Majority were detected by PET/CT (13/18 (72%)), with conventional CT scans missing the diagnoses otherwise made by PET/CT scans in 2/9 patients. Patients with type II EMCA were at higher risk of developing OM compared with patients with type I EMCA; 2/234 patients with type I EMCA (0.85%) developed OM, as compared to 16/167 patients with type II EMCA (9.58%), OR = 12.3. Patients with serous histology had significantly higher odds of developing OM when compared to patients with non-serous histologies (OR 4, p = 0.001, 95% CI 1.54 to 10.76). Kaplan Myer survival function and log-rank analysis showed that the presence of OM was a significant negative prognosticator of survival, with median overall survival (mOS) of 16 months in OM patients vs. mOS undefined in non-OM patients (p < 0.0001). DiscussionIncidence of detected OM was clinically significant, with most cases identified by PET/CT scans. Patients with type II EMCA, and in particular serous histology, were at a significantly higher risk of developing OM. OM when present, is an indicator of aggressive cancer biology and poor prognosis. Further studies are needed to ascertain the mechanism of predisposition to OM formation in serous EMCA and to confirm PET/CT as modality of choice for detection of OM.

PSMA PET total tumor volume predicts outcome of patients with advanced prostate cancer receiving [177Lu]Lu-PSMA-617 radioligand therapy in a bicentric analysis

Introduction[177Lu]Lu-PSMA-617 (Lu-PSMA) radioligand therapy is an emerging treatment option for patients with end-stage prostate cancer. However, response to Lu-PSMA therapy is only achieved in approximately half of patients. It is clinically important to identify patients at risk of poor outcome. Therefore, the aim of this study was to evaluate pretherapeutic PSMA PET derived total tumor volume and related metrics as prognosticators of overall survival in patients receiving Lu-PSMA therapy.MethodsA total number of 110 patients form the Departments of Nuclear Medicine Münster and Essen were included in this retrospective analysis. Baseline PSMA PET-CT was available for all patients. Employing a previously published approach, all tumor lesions were semi-automatically delineated in PSMA PET-CT acquisitions. Total lesion number, total tumor volume (PSMA-TV), total lesion uptake (PSMA-TLU = PSMA-TV * SUVmean), and total lesion quotient (PSMA-TLQ = PSMA-TV / SUVmean) were quantified for each patient. Log2 transformation was used for regressions.ResultsLesion number, PSMA-TV, and PSMA-TLQ were prognosticators of overall survival (HR = 1.255, p = 0.009; HR = 1.299, p = 0.005; HR = 1.326, p = 0.002). In a stepwise backward Cox regression including lesion number, PSMA-TV, PSA, LDH, and PSMA-TLQ, only the latter two remained independent and statistically significant negative prognosticators of overall survival (HR = 1.632, p = 0.011; HR = 1.239, p = 0.024). PSMA-TLQ and LDH were significant negative prognosticators in multivariate Cox regression in contrast to PSA value.ConclusionPSMA-TV was a statistically significant negative prognosticator of overall survival in patients receiving Lu-PSMA therapy. PSMA-TLQ was an independent and superior prognosticator of overall survival compared with PSMA-TV.

From Anemia to Erythropoietin Resistance in Head and Neck Squamous Cell Carcinoma Treatment: A Carousel Driven by Hypoxia.

Anemia has been identified as a significant negative prognosticator in head and neck squamous cell carcinoma (HNSCC) concurrent chemoradiotherapy (CCRT). Irrespective of the causes, anemia in HNSCC is believed to contribute to intratumoral hypoxia, which reduces the effectiveness of radiotherapy and oxygen-dependent chemotherapy. Correction of anemia with recombinant human erythropoietin (rHu-EPO) has been performed as a surrogate for hypoxia compensation to improve tumor control and survival outcomes. However, the results of the most important EPO clinical trials have been disappointing. Following the recent finding that EPO and its receptor (EPOR) are both expressed in HNSCC specimens, a new hypothesis has been advanced. This postulates that hypoxic signaling might activate EPOR through the hypoxia-inducible factor (HIF) signaling pathway and its downstream effectors, including carbonic anhydrase 9 (CA-9), glucose transporter 1 (GLUT-1), and vascular endothelial growth factor (VEGF), leading to the failure of rHu-EPO treatment, as assessed from the results of the best-known EPO trials. This review addresses the relationship among anemia, hypoxia, and tumoral EPO/EPOR expression in HNSCC treatment in an attempt to elucidate the main mechanisms involved in the resistance to rHu-EPO therapy, as in a carousel.

Programmed Death Ligand 1 Is a Negative Prognostic Marker in Recurrent Isocitrate Dehydrogenase-Wildtype Glioblastoma.

Checkpoint inhibition has demonstrated clinical efficacy in a variety of solid tumors. Reports of programmed death ligand 1 (PD-L1) expression in glioblastoma are highly variable (ranging from 6% to 88%) and its role as a prognostic marker has yielded conflicting results. To validate the prevalence and prognostic role of PD-L1 expression in a large cohort of diffuse gliomas according to the 2016 revised WHO classification. Using tissue microarrays, we compared 5 PD-L1 monoclonal antibodies (n=56) and validated expression (n=183) using quantitative immunohistochemistry (IHC) and RNA in situ hybridization (RISH). Expression data from The Cancer Genome Atlas (TCGA) and published studies were compared with clinical outcome. Multiplexed immunophenotyping was used to identify PD-L1+cell populations in post-treatment glioblastoma. Using a 5% cut-off, PD-L1 expression was significantly associated with a poor prognosis in both histologically defined (n=125, log-rank P<.001) and recurrent isocitrate dehydrogenase (IDH)-wildtype glioblastoma (n=60, log-rank P=.015). PD-L1 remained a significant negative prognosticator in Cox regression analysis (hazard ratio: 1.96, P=.021). Analysis of TCGA data confirmed decreased overall survival in recurrent non-glioma CpG island methylator phenotype (G-CIMP) glioblastoma (n=12, log-rank P=.023), but not in glioblastoma as a group (n=444, log-rank P=.135). PD-L1 RISH showed a significant correlation with IHC (P<.0001). PD-L1 was observed in the proliferating perivascular stem cell and immune niche of post-treatment glioblastoma. A 5% PD-L1 expression cut-off identified a subset of glioblastoma that is associated with a worse clinical outcome. This association remained significant within the newly defined IDH-wildtype classification. These findings could have implications for patient stratification in future clinical trials of PD-1/PD-L1 blockade.

97P - Pattern of first-site failure and salvage treatment in patients with inoperable stage III non-small cell lung cancer after chemoradiotherapy

Background: The standard of care treatment for inoperable stage III NSCLC is concurrent chemoradiotherapy (CRT) followed by consolidation with durvalumab. Loco-regional and distant recurrences remain common. Herein, we examine pattern of first-site failure and salvage treatment. Methods: We analysed the medical charts of 99 patients treated with CRT. Scans from date of first-site failure were fused with the delivered treatment plans. Recurrences were identified as in-field recurrence (IFR), out-of-field recurrence (OFR) [outside 50Gy isodose line] and distant metastases (DM). Using the Kaplan-Meier method with log-rank test for univariate analysis, the effect of salvage surgery (S), radiotherapy (sRT), chemotherapy (sCT) and immunotherapy (sIO) on overall survival (OS) was evaluated. Results: With a median follow-up of 17.2 months, the mOS for all patients was 20.8 months. 26 patients (26%) with IFR had a mOS of 19.3 months. In patients who survived at least 12 months from initial diagnosis (74%), IFR was a significant negative prognosticator (mOS 19.3 vs 40.0 months; p < 0.001). 25 (25%) patients developed OFR with no significant impact on survival (27.1 vs 20.8 months, p = 0.313). 3 (12%) patients with OFR underwent salvage surgery (p = 0.057) and were still alive at the time of this analysis. 5 (20%) patients underwent sRT with a mOS of 71.2 vs 19.1 months (p = 0.014). 13 (52%) patients with OFR received sCT; mOS 26.4 vs 32.7 mo. (p = 0.644;) and 4(16%) pts received sIO (mOS: 64.6 vs 26.4 months; p = 0.222). Distant and brain relapse were detected in 42 (42%) and 16 (16%) patients; mOS 19.1 vs. 22.9 months (p = 0.819) and 19.1 vs 20.8 mo. (p = 0.635), respectively. 15 (94%) patients with brain relapse received cranial radiotherapy: 7 (47%) whole brain irradiation and 8 (53%) stereotactic radiosurgery (mOS 15.3 vs. 37.8 mo.; p = 0.064). Conclusions: IFR was a significant negative predictor of OS in patients, who survived >1 year after initial diagnosis. Patients with OFR benefit most from salvage operation and/or radiotherapy. Furthermore, we observed survival benefit in patients who received SRS vs. WBRT for brain relapse. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Pretreatment prognostic factors of survival and late toxicities for patients with nasopharyngeal carcinoma treated by simultaneous integrated boost intensity-modulated radiotherapy

BackgroundTo scrutinize the pretreatment prognosticators on survival and late toxicities in a homogenous cohort of nasopharyngeal carcinoma (NPC) patients treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT).MethodsA total of 219 non-distant metastatic NPC patients consecutively treated by SIB-IMRT at a single institute were collected. The pretreatment factors including the socio-demographic variables, TNM stages, gross tumor volume (GTV), Epstein-Barr virus (EBV)-DNA, and hematologic inflammatory markers were analyzed. Cox model was used to screen the prognostic factors of late toxicities and four survival outcomes including locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS), and overall survival (OS).ResultsStatistically significant inter-correlations were observed between the values of EBV-DNA, some hematologic inflammatory markers, GTV, and N classification. The 5-year LRRFS, DMFS, FFS, and OS rates were 87.9%, 89.4%, 79.4%, and 81.3%, respectively. Multivariate analysis revealed that advanced N classification (N2–3 vs. N0–1) remained the only significant negative prognosticator for all the four survival outcomes. An increased monocyte percentage and a decreased lymphocyte-to-monocyte ratio were significantly associated with poorer FFS and OS, respectively. Larger GTV was observed to be predictive of poorer LRRFS. Patients with T3–4 (HR: 3.5, 95% CI: 1.0–12.1, p = 0.048) or higher GTV (HR: 1.006, 95% CI: 1.001–1.011, p = 0.027) were associated with higher incidence of radiation neuropathy.ConclusionN classification remains the most significant survival predictor for NPC patients treated by SIB-IMRT after adjusting these biomarkers. GTV impacts not only on locoregional control but also radiation neuropathy.

Survival Outcomes Improved in Contemporary Cohort of Patients With Pelvic or Abdominal Recurrence After Treatment for Stage I/II Endometrial Carcinoma

Pelvic and abdominal recurrences in stage I/II endometrial carcinoma are associated with poor outcomes, yet prognostic factors for survival after recurrence are not well described. Herein, we identify patients with pelvic or abdominal recurrence after surgery for stage I/II endometrial carcinoma and describe symptoms at presentation, prognostic factors, and salvage treatment toxicity. This is a retrospective cohort of 20 consecutively treated patients with recurrence after treatment for stage I/II endometrial carcinoma followed by our Institution's Radiation Oncology Department from 1998 to 2015. The median time to pelvic or abdominal recurrence was 18.1 months (range, 4.2 to 59.6 mo), with 50% of recurrences at extranodal locations. Two-year progression-free survival (PFS) was 44% and 2-year overall survival (OS) was 82%. Salvage treatments varied widely, including chemotherapy and radiotherapy (RT) (7), surgery and RT (3), and surgery, chemotherapy, and RT (3). On univariate analysis of PFS, symptoms at recurrence (P=0.04) and extranodal recurrences (P<0.01) were found to be statistically significant negative prognosticators for PFS. On univariate analysis of OS, increasing age at recurrence and presence of symptoms were found to have a trend toward statistically significant association with negative OS outcomes (P=0.08 and P=0.10, respectively). Our study demonstrates that long-term survival for pelvic or abdominal recurrences is possible with curative salvage therapy. The presence of symptoms is a negative prognostic factor in treatment outcome, and imaging may be effective for diagnosis in symptomatic and asymptomatic patients. Larger studies need to be performed to confirm these findings.

Investigation of RIP140 and LCoR as independent markers for poor prognosis in cervical cancer.

IntroductionRIP140 (Receptor Interacting Protein) is involved in the regulation of oncogenic signaling pathways and in the development of breast and colon cancers. The aim of the study was to analyze the expression of RIP140 and its partner LCoR in cervical cancers, to decipher their relationship with histone protein modifications and to identify a potential link with patient survival.MethodsImmunohistochemical analyses were carried out to quantify RIP140 and LCoR expression in formalin-fixed paraffin-embedded tissue sections cervical cancer samples. Correlations of RIP140 and LCoR expression with histopathological variables were determined by correlation analyses. Survival rates of patients expressing low or high levels of RIP140 and LCoR were compared by Kaplan-Meier curves.ResultsRIP140 overexpression was associated with a significantly shorter overall survival of cervical cancer patients. This effect was significant in the squamous cell carcinoma subtype but not in adenocarcinomas. RIP140 is no longer a significant negative prognosticator for cervical cancer when LCoR expression is low.DiscussionRIP140 is an independent predictor of poor survival of patients with cervical cancer. Patients with tumors expressing low levels of both RIP140 and LCoR showed a better survival compared to patients expressing high levels of RIP140. Modulation of RIP140 and LCoR may represent a novel targeting strategy for cervical cancer prevention and therapy.

Gamma Knife radiosurgery for medically and surgically refractory prolactinomas: long-term results.

Prolactinomas are the most common functioning pituitary adenomas. Dopamine agonists (DA) are generally very effective in treating prolactinomas by inducing tumor volume regression and endocrine remission. A minority of patients do not respond to DA or are intolerant because of side-effects. Microsurgical resection when possible is the next treatment option, but cavernous sinus, dural, or bone involvement may not allow for complete resection. We reviewed the outcome of patients with medically and surgically refractory prolactinomas treated with Gamma Knife radiosurgery (GKRS) during a 22years follow-up period. We reviewed the patient database at the University of Virginia Gamma Knife center during a 25-year period (1989-2014), identifying 38 patients having neurosurgical, radiological and endocrine follow-up. Median age at GKRS treatment was 43years. Median follow-up was 42.3months (range 6-207.9). 55.3% (n=21) were taking a dopamine agonist at time of GKRS. 63.2% (n=24) had cavernous sinus tumor invasion. Endocrine remission (normal serum prolactin off of a dopamine agonist) was achieved in 50% (n=19). GKRS induced hypopituitarism occurred in 30.3% (n=10). Cavernous sinus involvement was shown to be a significant negative prognosticator of endocrine remission. Taking a dopamine agonist drug at the time of GKRS showed a tendency to decrease the probability for endocrine remission. GKRS for refractory prolactinomas can lead to endocrine remission in many patients. Hypopituitarism is the most common side effect of GKRS.

Multi-reoperations for lung metastases.

In this study, we investigated role and results of multi-reoperations for lung metastases. From 1986 to 2010, 113 consecutive patients (61 men and 52 women; mean age: 53.2 ± 12.8 years) underwent repeated lung metastasectomy with curative intent in our institution. Two procedures were performed in 113 patients, three in 54, four in 31, five in eight and six in three. There was no perioperative mortality. Cumulative 5-year survival was 65% and this was significantly higher than the value recorded for patients undergoing only one metastasectomy (42%; p = 0.021). Size, number of resections and probability of recurrence increased by number of operation whereas disease free interval reduced. At any metastasectomy both short disease-free interval and multiple metastases resulted in the most significant negative prognosticators. In conclusion, redo metastasectomy is worthwhile for the initial procedures, afterwards both disease-free and overall survivals decrease and surgery lose its efficacy.

Prognostic factors in canine appendicular osteosarcoma – a meta-analysis

BackgroundAppendicular osteosarcoma is the most common malignant primary canine bone tumor. When treated by amputation or tumor removal alone, median survival times (MST) do not exceed 5 months, with the majority of dogs suffering from metastatic disease. This period can be extended with adequate local intervention and adjuvant chemotherapy, which has become common practice. Several prognostic factors have been reported in many different studies, e.g. age, breed, weight, sex, neuter status, location of tumor, serum alkaline phosphatase (SALP), bone alkaline phosphatase (BALP), infection, percentage of bone length affected, histological grade or histological subtype of tumor. Most of these factors are, however, only reported as confounding factors in larger studies. Insight in truly significant prognostic factors at time of diagnosis may contribute to tailoring adjuvant therapy for individual dogs suffering from osteosarcoma. The objective of this study was to systematically review the prognostic factors that are described for canine appendicular osteosarcoma and validate their scientific importance.ResultsA literature review was performed on selected studies and eligible data were extracted. Meta-analyses were done for two of the three selected possible prognostic factors (SALP and location), looking at both survival time (ST) and disease free interval (DFI). The third factor (age) was studied in a qualitative manner. Both elevated SALP level and the (proximal) humerus as location of the primary tumor are significant negative prognostic factors for both ST and DFI in dogs with appendicular osteosarcoma. Increasing age was associated with shorter ST and DFI, however, was not statistically significant because information of this factor was available in only a limited number of papers.ConclusionsElevated SALP and proximal humeral location are significant negative prognosticators for canine osteosarcoma.

Hepatic resection for metastatic colorectal adenocarcinoma: a proposal of a prognostic scoring system

Background: Hepatic resection for metastatic colorectal cancer provides excellent longterm results in a substantial proportion of patients. Although various prognostic risk factors have been identified, there has been no dependable staging or prognostic scoring system for metastatic hepatic tumors. Study Design: Various clinical and pathologic risk factors were examined in 305 consecutive patients who underwent primary hepatic resections for metastatic colorectal cancer. Survival rates were estimated by the Cox proportional hazards model using the equation: S( t)=[ S o ( t)] exp( R− R o ), where S o(t) is the survival rate of patients with none of the identified risk factors and R o = 0. Results: Preliminary multivariate analysis revealed that independently significant negative prognosticators were: (1) positive surgical margins, (2) extrahepatic tumor involvement including the lymph node(s), (3) tumor number of three or more, (4) bilobar tumors, and (5) time from treatment of the primary tumor to hepatic recurrence of 30 months or less. Because the survival rates of the 62 patients with positive margins or extrahepatic tumor were uniformly very poor, multivariate analysis was repeated in the remaining 243 patients who did not have these lethal risk factors. The reanalysis revealed that independently significant poor prognosticators were: (1) tumor number of three or more, (2) tumor size greater than 8 cm, (3) time to hepatic recurrence of 30 months or less, and (4) bilobar tumors. Risk scores (R) for tumor recurrence of the culled cohort (n = 243) were calculated by summation of coefficients from the multivariate analysis and were divided into five groups: grade 1, no risk factors (R = 0); grade 2, one risk factor (R = 0.3 to 0.7); grade 3, two risk factors (R = 0.7 to 1.1); grade 4, three risk factors (R = 1.2 to 1.6); and grade 5, four risk factors (R > 1.6). Grade 6 consisted of the 62 culled patients with positive margins or extrahepatic tumor. Kaplan-Meier and Cox proportional hazards estimated 5-year survival rates of grade 1 to 6 patients were 48.3% and 48.3%, 36.6% and 33.7%, 19.9% and 17.9%, 11.9% and 6.4%, 0% and 1.1%, and 0% and 0%, respectively (p < 0.0001). Conclusions: The proposed risk-score grading predicted the survival differences extremely well. Estimated survival as determined by the Cox proportional hazards model was similar to that determined by the Kaplan-Meier method. Verification and further improvements of the proposed system are awaited by other centers or international collaborative studies.

Treatment of the Septic Hip with Total Hip Arthroplasty

Forty-three patients, 23 with definite infection and 20 with probable infections before total hip arthroplasty (THA), were compared to 41 matched uninfected patients. The 43 infected patients were treated by 45 operative procedures: eight Girdlestone resections, 12 revisions of total hips, and 25 conversions from infected nontotal hip surgery to total hip arthroplasties. (Two revision THAs were converted to Girdlestones). The average follow-up period was 38.8 months, with a range of six-118 months. The statistically significant negative prognosticators were gross sepsis at surgery, number of previous operations, and elevated erythrocyte sedimentation rate (ESR). The type of infecting organism did not affect the outcome. The prosthesis survival rate for total hip arthroplasties revised for sepsis was 83%. The prosthesis survival rate for other infected hips treated by total hip arthroplasty was 100%. All groups except Girdlestone resections improved postoperatively. While Girdlestone resection offered acceptable pain relief, total hip arthroplasty provided unequivocally superior function (p = 0.0001).