Treatment-related Prognostic Factors Research Articles

Initial local resection versus early referral for spermatic cord sarcoma: Any impact on treatment timelines and oncological outcomes?

ObjectivesSpermatic cord sarcomas are exceedingly rare, often misdiagnosed and subsequently improperly treated at local hospitals. This retrospective study looked at the oncological outcomes of spermatic cord sarcoma cases managed with curative intent resection at a tertiary referral sarcoma centre. We specifically studied how initial inadequate resections impact the oncologic outcomes compared to primary tumour resections at the reference centre. MethodsOne hundred eighteen consecutive patients affected by primary, localized spermatic cord sarcoma surgically managed at our reference centre from January 2001 through January 2021 were included. Primary endpoints were local relapse free (LRFS), distant metastasis free (DMFS) and overall survival (OS). These outcomes were evaluated with multi-nomial logistic regression and Cox proportional hazards regression models for a co-relation to known patient, tumour and treatment-related prognostic factors, including a prior inadequate resection and time from diagnosis to a complete oncologic resection as independent variables. Secondarily, we compared the above variables and treatment intervals among the subgroups of primary versus re-resection surgery. ResultsOver a median follow-up of 54 months (IQR 25–105), 12 patients (10.2%) developed local recurrence (LR) and 14 (11.6%) had distant metastasis (DM). 5-year local relapse (LRFS) and distant metastasis-free survival (DMFS) were 89.3% and 86.5%, respectively. Higher tumour grade and size were associated with a worse DMFS (p=<0.05). Likewise, marginal (R1) resection correlated with an inferior LRFS (p=< 0.05).Eighty-four patients (71.2%) had their initial diagnosis established on an inadequate surgical excision performed in a local hospital, followed by a re-excision at our centre (Re-resection group). During the same period, 34 (28.8%) were managed primarily with biopsy and treatment at our reference centre (Primary-resection group). The two groups had statistically significant differences in tumour size, histopathology, surgery duration, rate of postoperative complication and R0 resection (p < 0.005). Additionally, the difference in time intervals to achieve the treatment targets was statistically insignificant and did not correlate to the risk of recurrence as an independent variable. Residual disease was present in 51.2 % (n = 43) of the re-excision specimens. However, following a complete R0 resection, this did not correlate with a higher risk of recurrence (p = 0.481). ConclusionPrompt referral to a tertiary centre, where multidisciplinary evaluation and sound oncologic resections are the standard of treatment, can align the OS and DFS of patients receiving incomplete surgery elsewhere to those treated primarily in referral centres. The primary determinant of prognosis remains surgical margin, tumour size and grade.

The Outcome of Anaplastic Glioma Treated at a Tertiary Cancer Care Institute in South Asia

Objective: Anaplastic glioma is a highly aggressive brain tumor that often occurs in young adults. There is a lack of data from India on anaplastic gliomas. This study aims to evaluate the prognostic factors of anaplastic glioma and correlate them with the outcome. Materials and Methods: This is a retrospective observational study of 57 patients with anaplastic glioma treated from 1996 to 2015 in a cancer institute in Chennai. We captured data from the cancer institute’s hospital-based electronic health record tumor registry and correlated factors including age, sex, histology, site of disease, type of surgery, adjuvant treatment, and radiation treatment technique with outcome. For the calculation of progression-free survival (PFS) and Overall Survival (OS), we used Statistical Package for Social Science (SPSS) software. Result: This analysis included fifty-seven patients, with a median follow-up of 34 months. The median progression-free survival (PFS) and overall survival (OS) were 28 and 41 months, respectively. On univariate analysis, factors associated with improved survival include Anaplastic Oligodendroglioma histology (HR-0.43, CI-0.22-0.80, P=0.006), Frontal lobe location (HR-1.96, CI-1.07-3.58, P=0.025) Gross total resection (HR-1.94, CI-1.03-3.64, P=0.034), and addition of Temozolamide (HR-2.09, CI-1.14-3.84, P=0.014). On multivariate analysis Anaplastic Oligodendroglioma histology, (HR-0.49,CI-0.25-0.95,P=0.037), Frontal lobe (HR-2.14,CI-1.12-4.07,P=0.021), Gross total resection (HR-2.89,CI-1.47-5.69,P=0.002) and addition of Temozolamide (HR-2.02,CI-1.07-3.81,P=0.029) remained significant factors for improved OS. Conclusion: Among the various clinical and treatment-related prognostic factors, our study revealed that anaplastic oligodendroglioma histology, frontal lobe location, gross total resection, and addition of temozolomide chemotherapy to radiation showed improved outcomes.

Treatment outcome of IDH1/2 wildtype CNS WHO grade 4 glioma histologically diagnosed as WHO grade II or III astrocytomas

BackgroundIsocitrate dehydrogenase (IDH)1/2 wildtype (wt) astrocytomas formerly classified as WHO grade II or III have significantly shorter PFS and OS than IDH mutated WHO grade 2 and 3 gliomas leading to a classification as CNS WHO grade 4. It is the aim of this study to evaluate differences in the treatment-related clinical course of these tumors as they are largely unknown.MethodsPatients undergoing surgery (between 2016–2019 in six neurosurgical departments) for a histologically diagnosed WHO grade 2–3 IDH1/2-wt astrocytoma were retrospectively reviewed to assess progression free survival (PFS), overall survival (OS), and prognostic factors.ResultsThis multi-center study included 157 patients (mean age 58 years (20–87 years); with 36.9% females). The predominant histology was anaplastic astrocytoma WHO grade 3 (78.3%), followed by diffuse astrocytoma WHO grade 2 (21.7%). Gross total resection (GTR) was achieved in 37.6%, subtotal resection (STR) in 28.7%, and biopsy was performed in 33.8%. The median PFS (12.5 months) and OS (27.0 months) did not differ between WHO grades. Both, GTR and STR significantly increased PFS (P < 0.01) and OS (P < 0.001) compared to biopsy. Treatment according to Stupp protocol was not associated with longer OS or PFS compared to chemotherapy or radiotherapy alone. EGFR amplification (P = 0.014) and TERT-promotor mutation (P = 0.042) were associated with shortened OS. MGMT-promoter methylation had no influence on treatment response.ConclusionsWHO grade 2 and 3 IDH1/2 wt astrocytomas, treated according to the same treatment protocols, have a similar OS. Age, extent of resection, and strong EGFR expression were the most important treatment related prognostic factors.

Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review

BackgroundImmune-suppressing drugs can cause liver, kidney or blood toxicity. Prognostic factors for these adverse-events are poorly understood.PurposeTo ascertain prognostic factors associated with liver, blood or kidney adverse-events in people receiving...

Comparison of Low Dose Rate and High Dose Rate Brachytherapy Boost Techniques in Prostate Cancer: Evaluation of Toxicity.

The ASCENDE-RT trial has been criticized for higher rates of chronic severe toxicity (18% genitourinary (GU)) than expected with a low dose rate (LDR) boost technique. We compared clinical outcomes of LDR and high dose rate (HDR) boost in the acute and chronic setting from a large single institution experience over a continuous 20-year period, with a focus on GU and gastrointestinal (GI) toxicity during treatment of prostate cancer. We retrospectively reviewed patients treated with LDR boost (2003 - 2013) and HDR boost (2014 - 2018). Clinical and treatment-related prognostic factors including age, stage, androgen deprivation therapy (ADT), dosimetry details, and toxicity data were recorded. Toxicity was scored according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Multi-variable analysis (MVA) was performed to evaluate variables associated with toxicity. A total of 184 men were evaluated (87 LDR and 97 HDR) with a median follow-up of 7.1 years and 4.0 years, respectively. Most patients (92% LDR and 57% HDR) received ADT in addition to BT. The median EBRT dose was 46 Gy for LDR and 45 Gy for HDR (range 25 - 50 Gy). Prostate D90% was similar at 104% and 105% in the LDR and HDR groups, respectively. Urethra D10% and Rectum V100% were both higher with LDR compared to HDR with 155% vs 119% and 0.436% vs 0.073%, respectively. Severe (grade 3+) toxicity was rare (Table 1), with 3.4% of LDR patients experiencing grade 3 chronic GU toxicity. With HDR, 3.1% and 1% of patients experienced acute and chronic grade 3 GU toxicity, respectively. Although non-severe GU toxicity (grade 1-2) was similar between groups (95% LDR vs 89% HDR, p = 0.16), LDR patients experienced more grade 2 GU events (80.5% acute; 82.8% chronic) compared to HDR patients (45.4% acute; 57.7% chronic). There were no severe GI toxicities in the acute or chronic period. Non-severe acute GI toxicity was more common with HDR, while non-severe chronic GI toxicity was more common with LDR. On MVA, acute GU toxicity (any grade) was associated with short term ADT (p = 0.01) and Urethra D10% (p < 0.05); Chronic GU toxicity (any grade) was associated with age (p = 0.09) and Prostate V150cc (p = 0.07) but not BT boost technique. This comparative retrospective analysis of BT boost techniques reveals the overall rate of severe GU and GI toxicity to be low with both LDR and HDR. HDR boost appears to have a slightly more favorable ratio of Grade 1 to Grade 2 GU toxicity and improved urethra/rectum dosimetry. Our analysis suggests that the dosimetric advantages of HDR may deliver small reductions in GU toxicity.

Reirradiation of head and neck squamous cell carcinomas: a pragmatic approach-part I: prognostic factors and indications to treatment.

Reirradiation (reRT) of locally recurrent/second primary tumors of the head and neck region is a potentially curative treatment for patients not candidate to salvage surgery. Aim of the present study is to summarize available literature on both prognostic factors and indications to curative reRT in this clinical setting. A narrative review of the literature was performed on two topics: (1) patients' selection according to prognostic factors and (2) dosimetric feasibility of reRT. Postoperative reRT and palliative intent treatments were out of the scope of this work. Patient-tumor and treatment-related prognostic factors were analyzed, together with dosimetric parameters concerning target volume and organs at risk. Based on available evidence, a stepwise approach has been proposed aiming to provide a useful tool to identify suitable candidates for curative reRT in clinical practice. This was then applied to two clinical cases, proposed at the end of this work. A second course of RT in head and neck recurrence/second primary tumors is a personalized approach that can be offered to selected patients only in centers with expertise and dedicated equipment following a multidisciplinary team discussion.

Pathologic Nodal Staging Before SBRT for Early-stage NSCLC Does Not Impact Overall Survival: A Propensity Score-matched NCDB Analysis.

Stereotactic body radiation therapy (SBRT) for early-stage non-small cell carcinoma of the lung (NSCLC) is increasingly utilized. We sought to assess overall survival (OS) for early-stage NSCLC patients receiving SBRT depending on staging method. Early-stage NSCLC patients treated with definitive SBRT were identified in the National Cancer Database (NCDB), and OS was determined based on method of staging. Patient, disease, and treatment characteristics were also analyzed. A total of 12,106 patients were included; 865 (7%) received invasive staging (nodal sampling, NS) and 11,241 (93%) had no nodal sampling (NNS). From this larger dataset, a propensity score matching (1:1 without replacement) was performed, which yielded 839 patients for each group (NNS and NS). With a median follow-up time of 3.12 years, median survival for all patients included in the matched dataset was 2.75 years (95% CI: 2.55-2.93y), with 2- and 5-year OS estimated at 63.9% and 25.7%, respectively. In a multivariable analysis on matched data, there was no difference in mortality risk between the NNS and NS groups (hazard ratio=1.08, 95% CI: 0.94-1.24, P =0.25). Negative prognostic factors identified in the multivariable analysis of the matched data included: age more than 65, male sex, Charlson-Deyo Score ≥1, and tumor size ≥3cm. SBRT use in early-stage NSCLC steadily increased over the study period. Most patients proceeded to SBRT without nodal staging, conflicting with National Comprehensive Cancer Network (NCCN) guidelines which recommend pathologic mediastinal lymph node evaluation for all early-stage NSCLC cases, except stage IA. Our findings suggest similar OS in patients with early-stage NSCLC treated with SBRT irrespective of nodal staging. Furthermore, we highlight patient-related, disease-related, and treatment-related prognostic factors to consider when planning therapy for these patients.

SDPS-37 IDENTIFICATION OF TIME-COURSE RELATED, TREATMENT-RELATED, AND PATIENT-RELATED PROGNOSTIC FACTORS IN BRAF-MUTANT MELANOMA BRAIN METASTASES.

Abstract PURPOSE Patients with BRAF-mutant melanoma brain metastases (MBM) continue to have limited overall survival (OS), averaging 4 months, despite advancements in systemic therapies. Our study aims to identify patient-specific and treatment-related prognostic factors in BRAF-mutant MBM to inform treatment sequencing and patient selection in future studies and improve patient outcomes. METHODS The following data were manually curated from 100 patients with BRAF-mutant MBM diagnosed from 2009-2018, with primary cutaneous melanoma and who received initial MBM treatment at our institution: clinical and demographic, treatment, and OS outcomes. We compared OS with the log rank test using the Python package kaplanmeier between the various clinical, demographic and treatment (including treatment sequence) related variables. RESULTS Both elevated lactase dehydrogenase (LDH) was associated with shorter OS (p=0.023), as was leptomeningeal disease (p&amp;lt;0.001). Gender (male vs. female) and initial treatment modality (BRAFi vs. immunotherapy) did not significantly impact OS, (p=0.911 and 0.578, respectively). Breakthrough brain metastases were associated with shorter OS for patients who received initial systemic therapy for MBM (p&amp;lt;0.001), but breakthrough metastases did not significantly impact OS for the whole cohort (p=0.141). Additionally, patients who received BRAFi before MBM diagnosis had shorter OS (p=0.028). CONCLUSION In conclusion, we have identified some interesting relationships between OS and the sequencing of treatment modalities, as well as the timing of MBM presentation. These findings support further investigation of treatment sequencing to improve outcomes and the consideration of clinical variables, disease presentation, and treatment history to help refine patient selection for future trials for patients with BRAF-mutant MBM.

Impact of various prognostic factors on survival in glioblastoma: tertiary care institutional experience.

IntroductionGlioblastoma is the most common malignant brain tumour in adults. Among all gliomas, it is the most aggressive type, with a high fatality rate, and according to the WHO classification, it is a grade IV tumour. As this tumour is well-known for its poor survival, an understanding of clinical and treatment-related prognostic factors can help in tailored treatment. The aim of this study was to know the impact of prognostic factors on survival in these cases.Materials and methodsAll glioblastoma patients treated in our hospital during 2010–2015 were included in the analysis. Cases were divided into different groups based on prognostic factors. Overall survival (OS) and disease-free survival (DFS) were calculated and compared among the different groups. Statistical analysis was carried out using SPSS software v20.ResultsOne-year OS was 36.9% and 2-year OS was 10.8%. One-year DFS was 13.04%. On univariate analysis, age at presentation ≤45 years and adjuvant chemotherapy with six cycles or more temozolomide improved OS and DFS. Multivariate analysis retained the statistically significant positive impact of usage of adjuvant temozolomide chemotherapy of ≥six cycles on OS and DFS. The use of the anti-epileptic drug Levetiracetam had a statistically significant improvement of DFS.ConclusionAmong various clinical and treatment-related prognostic factors evaluated in our study, younger age at presentation and addition of temozolomide chemotherapy to radiation showed improvement in OS and DFS. The use of the anti-epileptic drug Levetiracetam had an impact on DFS in glioblastoma patients.

Clinical phenotypes and prognostic features of embryonal tumours with multi-layered rosettes: a Rare Brain Tumor Registry study

Embryonal tumours with multi-layered rosettes (ETMRs) are a newly recognised, rare paediatric brain tumour with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and scarce clinical data, disease features and determinants of outcomes for these tumours are poorly defined. We did an integrated clinicopathological and molecular analysis of primary ETMRs to define clinical phenotypes, and to identify prognostic factors of survival and key treatment modalities for this orphan disease. Paediatric patients with primary ETMRs and tissue available for analyses were identified from the Rare Brain Tumor Consortium global registry. The institutional histopathological diagnoses were centrally re-reviewed as per the current WHO CNS tumour guidelines, using histopathological and molecular assays. Only patients with complete clinical, treatment, and survival data on Nov 30, 2019, were included in clinicopathological analyses. Among patients who received primary multi-modal curative regimens, event-free survival and overall survival were determined using Cox proportional hazard and log-rank analyses. Univariate and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) with 95% CIs for clinical, molecular, or treatment-related prognostic factors. 159 patients had a confirmed molecular diagnosis of primary ETMRs (median age at diagnosis 26 months, IQR 18-36) and were included in our clinicopathological analysis. ETMRs were predominantly non-metastatic (94 [73%] of 128 patients), arising from multiple sites; 84 (55%) of 154 were cerebral tumours and 70 (45%) of 154 arose at sites characteristic of other brain tumours. Hallmark C19MC alterations were seen in 144 (91%) of 159 patients; 15 (9%) were ETMR not otherwise specified. In patients treated with curative intent, event-free survival was 57% (95% CI 47-68) at 6 months and 31% (21-42) at 2 years; overall survival was 29% (20-38) at 2 years and 27% (18-37) at 4 years. Overall survival was associated with non-metastatic disease (HR 0·48, 95% CI 0·28-0·80; p=0·0057) and non-brainstem location (0·42 [0·22-0·81]; p=0·013) on univariate analysis, as well as with gross total resection (0·30, 0·16-0·58; p=0·0014), high-dose chemotherapy (0·35, 0·19-0·67; p=0·0020), and radiotherapy (0·21, 0·10-0·41; p<0·0001) on multivariable analysis. 2-year event-free and overall survival was 0% at 2 years in patients treated with conventional chemotherapy without radiotherapy (regardless of surgery extent), and 21% (95% CI 1-41) and 30% (6-54), respectively, in patients treated with high-dose chemotherapy, and gross total resection without radiotherapy. 2-year event-free survival in patients treated with high-dose chemotherapy and radiotherapy was 66% (95% CI 39-93) for patients with gross total resection and 44% (7-81) for patients with sub-total resection. 2-5-year overall survival was 66% (95% CI 33-99, p=0·038) for patients with gross total resection and 67% (36-98, p=0·0020) for patients with sub-total resection. Prompt molecular diagnosis and post-surgical treatment with intensive multi-modal therapy tailored to patient-specific risk features could improve ETMR survival. Canadian Institute of Health Research, Canada Research Chair Awards, Australian Lions Childhood Cancer Research Foundation, Spanish Society of Pediatrics, Consejería de Salud y Familias de la Junta de Andalucía, Miracle Marnie, Phoebe Rose Rocks, Tali's Funds, Garron Cancer Centre, Grace's Walk, Meagan's Hug, Brainchild, Nelina's Hope, and Jean Martel Foundation.

Improved oncologic outcomes by ablative radiotherapy in patients with bone metastasis from hepatocellular carcinoma.

For bone metastasis from hepatocellular carcinoma (HCC), radiotherapy (RT) has been used a palliative treatment with little impact on survival. Currently, ablative RT is popularly used, and a more than palliative effect is expected. Herein, we investigated the clinical efficacy of ablative RT in patients with bone metastasis from HCC. In total, 530 patients with 887 lesions treated in 1992-2019 were reviewed. Oligometastasis was defined as the presence of < 5 lesions. Total doses were normalized to obtain biologically effective doses (BEDs). The cut-off threshold of the BED was determined via receiver operating characteristics curve analysis. The Kaplan-Meier method was used to calculate overall survival (OS); propensity score matching (PSM) was performed to balance the heterogeneity in cases while comparing BEDs of ≥ 60 and < 60Gy. The most common site of metastasis was the spine (59%); 59 patients (11%) presented with oligometastasis, and 76.2% of patients showed objective pain palliation after RT. Median OS was 5.1months for all patients; patients with oligometastasis showed longer OS than those without (9.8 vs. 4.7months). A Cox proportional hazards model showed that performance status, Child-Pugh class, extraosseous metastasis, primary HCC status, α-fetoprotein level, and radiation dose (BED) were significant prognostic factors. Post PSM, BED was the only treatment-related prognostic factor that remained significant; the median OS durations were 8.1 and 4.4months when the BEDs were ≥ 60 and < 60Gy, respectively. Ablative RT improved OS and pain palliation in patients with bone metastasis from HCC.

Survival outcomes of surgery in patients with pulmonary large-cell neuroendocrine carcinoma: a retrospective single-institution analysis and literature review

BackgroundPulmonary large-cell neuroendocrine carcinoma (pLCNEC) is a very rare malignancy originating from the lung and bronchus, and its biological behaviour, clinical diagnosis, treatment and prognosis are poorly understood. Thus, the clinical characteristics and surgical treatment-related prognostic factors of this rare disorder must be explored.ResultsThe clinical data of 59 patients (48 males and 11 females) who were treated by surgery and diagnosed with pLCNEC by postoperative pathology at Peking Union Medical College Hospital from April 2004 to April 2019 were analysed retrospectively. The median patient age was 62 years (38–79 years), and the median duration of disease was 2 months (0.5–18 months). Compared with other lung malignancies, pLCNEC lacks specific clinical symptoms and imaging features, and preoperative biopsy pathology is often insufficient to confirm the diagnosis. The corresponding numbers of patients who were classified into stages I, II, III and IV according to the postoperative pathological tumour-nodal-metastasis stage were 25, 12, 15 and 7, respectively. The median overall survival was 36 months (0.9–61.1 months). The 1-year, 3-year and 5-year survival rates were 76.3%, 49% and 44.7%, respectively. The tumour stage exerted a significant effect on survival (Cox multivariate analysis p < 0.05).ConclusionsFor patients with resectable pLCNEC, multidisciplinary therapy based on surgery may have good survival benefits, and tumour stage is an independent risk factor for the prognosis of pLCNEC.

A BMI-category distribution pattern of intrinsic and treatment-related prognostic factors in endometrial cancer

In patients with endometrial cancer, obesity is associated with favorable prognostic characteristics but not with prolonged survival. The aim of this study was to elucidate the reason for this clinical paradox. We retrospectively reviewed 1173 patients with endometrial cancer. Patients were divided into a non-obese group [body mass index (BMI)<30kg/m2], class I obesity group (BMI 30-35kg/m2) and class II obesity group (BMI≥35kg/m2). The relationship between clinicopathological factors and disease-specific survival (DSS) was analyzed by Cox regression analysis. To correct for three-time significance testing, we used the Bonferroni method, giving the level of probability at which findings were considered significant as P<0.0167. Three disease-intrinsic variables-older age, advanced stage and high-risk histology-and three treatment-related variables-no hysterectomy, no lymphadenectomy and no chemotherapy-were independently associated with poor DSS. DSS was similar among the three groups of patients even though the proportion of patients with plural pretreatment-related unfavorable risk factors significantly decreased with increment of BMI category (40.1 vs. 27.5 vs. 17.6%, P=0.0003). The proportion of patients with plural treatment-related unfavorable prognostic factors significantly increased with increment of BMI category (21.3 vs. 26.7 vs. 39.3%, P=0.0072). Poor-quality surgical staging in obese women may result in worse than expected survival outcomes.

Comprehensive analysis of patient outcome after local recurrence of locally advanced cervical cancer treated with concomitant chemoradiation and image-guided adaptive brachytherapy

IntroductionSince dose escalation allowed by image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer (LACC), local relapses have become a rare event. Only scarce data are available on the outcome of patients experiencing a local relapse after IGABT. MethodsBetween 2004 and 2016, all consecutive patients treated at Gustave Roussy Institute for LACC and receiving concomitant chemoradiation and IGABT were analysed. Clinical and treatment-related prognostic factors for survival after local relapse were searched, in order to potentially identify patients requiring salvage treatment. ResultsTwo hundred and fifty-nine patients were treated during this period. With a median follow-up of 4.1 years, 10.8% (n = 28) had a local relapse. Among these patients, 53.6% had synchronous lymph nodes or distant metastatic relapse and only 13 patients (5% of all patients) had isolated local relapse. After local relapse, median survival was 47 months and three patients were alive at last follow-up. Only three patients with local relapse could receive salvage surgery (10.7%). Metastases occurrence and pelvic wall involvement were the main contraindications (67.9%) for salvage surgery. Among the three patients treated with surgery, two are still alive at last follow-up without significant complication. Improved survival was observed among the two patients who could have surgery (p = .02). Local progression led to serious symptoms in 75% of patients. Only the time interval between brachytherapy and relapse (<1 year) was prognostic for 2-year overall survival (p = .005). ConclusionSalvage surgery is feasible in a very low number of highly selected patients with local relapse following IGABT. Local failure is a major cause of severe local symptoms, confirming that every effort should be done to achieve long-term local control through dose escalation.

Surgery for stage IV gastric cancer: An Italian perspective.

403 Background: Surgical approach to gastric cancer with hepatic metastases is becoming more and more accepted but few information exist concerning the surgical management of gastric cancer with extra-hepatic metastases. With this retrospective study we evaluated if the prognosis is influenced by different metastatic sites and we looked for the presence of prognostic factors. Methods: We analysed 282 patients with gastric cancer and synchronous metastases treated at our Institutions from 2010 to January 2017. We investigated survival performances after surgery according to the site of metastases: peritoneal, haematogenous, hepatic, distant lymph nodes and more than one site. Furthermore, we investigated how survival was influenced by patient-, gastric cancer-, metastases- and treatment-related prognostic factors. Results: Median overall survival was 10.9 months. We found no survival differences according to the site of metastases: median survival was 11.2, 11.6, 9.8, 21.4, 7.0 months for peritoneal, hepatic, lymph-nodal, haematogenous and more than1 site of metastases, respectively (p = 0.797). In all subgroups we observed an interesting number of long-term survivors (peritoneal 14.3% ≥36 months, 7.6% ≥60 months; hepatic 13.0% ≥36 months, 2.2% ≥60 months; lymph nodes 12.5% ≥36 months, 3.1% ≥60 months; &gt; 1 site 18.7% ≥36 months, 1.6% ≥60 months). At multivariate analysis the factors that influenced survival were: number of resected lymph-nodes (p = 0.013), extension of lymphadenectomy (p &lt; 0.001), pN (p = 0.003), curativity (p = 0.032) and histology (p = 0.028). Conclusions: We showed that no differences in overall survival according to site of metastases exist and we suggest that patients in whom a curative resection is possible, should be treated by resection of both gastric cancer and metastases.

Impact of chemotherapy cycles and intervals on outcomes of nonspinal Ewing sarcoma in adults: a real-world experience

BackgroundAdult Ewing sarcoma (ES) is a rare disease, the optimal treatment model is unknown. This study aimed to retrospectively analyze treatment-related prognostic factors of nonspinal ES in Chinese adults.MethodsEighty-one patients treated between January 2005 and December 2017 were included in the present study. Thirty-three (40.7%) presented with metastatic disease at diagnosis. Eight patients were submitted to primary surgery followed by chemotherapy, while 73 patients received chemotherapy before and after surgery and/or local radiotherapy. The chemotherapy regimen included 8–17 cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE) every 3 weeks. Clinical outcomes and safety were analyzed.ResultsVDC/IE chemotherapy was well tolerated in adult patients with ES. Multivariate Cox regression analyses revealed that chemotherapy of at least 12 cycles was a favorable independent prognostic factor of event-free survival (hazard ratio, 0.558; 95% confidence interval, 0.323–0.965; P = 0.037) and overall survival (hazard ratio, 0.424; 95% confidence interval, 0.240–0.748; P = 0.003). Similarly, a low frequency of chemotherapy delays was an independent prognostic factor of improved OS (hazard ratio, 0.438; 95% confidence interval, 0.217–0.887; P = 0.022).ConclusionOur study suggests that adults with ES should be treated with an aggressive multidisciplinary approach, intensive chemotherapy with adequate cycles and appropriate intervals can be recommended in this group.

Treatment-Related Prognostic Factors in Managing Osteosarcoma around the Knee with Limb Salvage Surgery: A Lesson from a Long-Term Follow-Up Study.

Purpose The aim of this study was to assess the treatment-related factors associated with local recurrence and overall survival of patients with osteosarcoma treated with limb-salvage surgery. Patients and Methods Treatment-related factors were analyzed to evaluate their effects on local recurrence-free survival (LRFS) and overall survival (OS) in 182 patients from 2004 to 2013. Results The mean length of follow-up was 73.4 ± 34.7 months (median, 68 months; range, 12-173 months), and 63 patients died by the end of the follow-up. The 5-year and 10-year overall survival rates were 68.6 ± 6.6% and 59.4 ± 10.6%, respectively. Univariate analysis showed that treatment-related prognostic factors for overall survival were prolonged symptom intervals >=60 days, biopsy/tumor resection performed by different centers, previous medical history, incomplete preoperative chemotherapy (<8 weeks), and prolonged postoperative interval >21 days. In the multivariate analysis, biopsy/tumor resection performed by different centers, incomplete implementation of planned new adjuvant chemotherapy, and delayed resumption of postoperative chemotherapy (>21 days) were risk factors for poor prognosis; biopsy/tumor resection performed by different centers and tumor necrosis <90% were independent predictors of local recurrence. Conclusion For localized osteosarcoma treated with limb-salvage surgery, it is necessary to optimize timely standard chemotherapy and to resume postoperative chemotherapy to improve survival rates. Biopsies should be performed at experienced institutions in cases of developing local recurrence.

Prognostic factors for survival in stage IV rectal cancer: A Swedish nationwide case–control study

PurposeThe aim was to identify patient-, tumor- and treatment-related prognostic factors for five-year survival in rectal cancer patients with synchronous stage IV disease. Material and methodsThis nationwide case-control study was based on the Swedish Colorectal Cancer Registry with supplementary information from medical records and the Swedish Inpatient Registry during the period 2000–2008. All resected rectal cancer patients with synchronous metastases that survived more than five years were included as cases. The control group consisted of corresponding patients who lived less than five years, matched in a 1:2 based on gender, age, resection of the rectal tumor, and the study period. ResultsA total of 405 patients were identified; 99 long-term survivors (LTS) and 182 short-term survivors (STS). Patient-related factors of symptoms and comorbidity did not differ between LTS and STS. Among the treatment-related factors, multiple site metastases (p = 0.007), bilobar liver metastasis (p = 0.002), and increasing number of liver metastasis (p < 0.001) were associated with STS. Prognostic treatment-related factors were preoperative radiotherapy (p = 0.001), metastasectomy (p < 0.001), and radical resection of the primary tumor (p = 0.014). In the multivariable analysis, the single most important factor for becoming a LTS was a metastasectomy (hazard ratio: 8.474, 95% confidence interval: 4.098–17.543). ConclusionsThe most important prognostic factor for long-term survival in patients with stage IV rectal cancer was metastasectomy, especially liver surgery. With thorough selection of patients for metastasectomy more patients with metastasized rectal cancer may survive beyond five years.

Surgical treatment of hepatic metastases from gastric cancer.

The purpose of the study was to investigate the clinical factors influencing the prognosis of patients submitted to hepatectomy for metastases from gastric cancer and their clinical role. We conducted a retrospective multicentre review. We evaluated how survival from surgery was influenced by patient-related, tumour-related and treatment-related prognostic factors. We analysed data on 144 patients submitted to hepatectomy for metastases from gastric cancer, in the synchronous and metachronous setting. In 117 cases, an R0 resection was achieved, while in 27 an R + hepatic resection was performed. Chemotherapy was administered to 55 patients. Surgical mortality was 2.1% and morbidity 21.5%. One-, 3-, and 5-year OS rates after surgery were 49.9, 19.4 and 11.6%, respectively, with a median OS of 12.0months. T4 gastric cancer, H3 hepatic involvement, non-curative resection, recurrence after surgery, and abstention from chemotherapy were associated with a worse prognosis. Factor T and H displayed a clear (p < 0.001) cumulative effect. Our data show that R0 resection must be pursued whenever possible. The treatment of T4 gastric cancer with hepatic bilateral and diffuse metastasis (H3) should be considered carefully or it should be probably avoided. Finally, a multimodal treatment associating surgery and chemotherapy offers the best survival results.

Treatment-Related Predictive and Prognostic Factors in Trimodality Approach in Stage IIIA/N2 Non-Small Cell Lung Cancer

While there are no established pretreatment predictive and prognostic factors in patients with stage IIIA/pN2 non-small cell lung cancer (NSCLC) indicating a benefit to surgery as a part of trimodality approach, little is known about treatment-related predictive and prognostic factors in this setting. A literature search was conducted to identify possible treatment-related predictive and prognostic factors for patients for whom trimodality approach was reported on. Overall survival was the primary endpoint of this study. Of 30 identified studies, there were two phase II studies, 5 “prospective” studies, and 23 retrospective studies. No study was found which specifically looked at treatment-related predictive factors of improved outcomes in trimodality treatment. Of potential treatment-related prognostic factors, the least frequently analyzed factors among 30 available studies were overall pathologic stage after preoperative treatment and UICC downstaging. Evaluation of treatment response before surgery and by pathologic tumor stage after induction therapy were analyzed in slightly more than 40% of studies and found not to influence survival. More frequently studied factors—resection status, degree of tumor regression, and pathologic nodal stage after induction therapy as well as the most frequently studied factor, the treatment (in almost 75% studies)—showed no discernible impact on survival, due to conflicting results. Currently, it is impossible to identify any treatment-related predictive or prognostic factors for selecting surgery in the treatment of patients with stage IIIA/pN2 NSCLC.