First-line Treatment Modalities Research Articles

Evaluation of the efficacy and safety of first- and second-line immunotherapy in patients with metastatic colorectal cancer: a systematic review and network meta-analysis based on randomized controlled trials

BackgroundA multitude of randomized controlled trials (RCTs) conducted in both the initial and subsequent treatment settings for patients diagnosed with metastatic colorectal cancer (mCRC) have provided clinical evidence supporting the efficacy of immunotherapy with the use of immune checkpoint inhibitors (ICIs). In light of these findings, the U.S. Food and Drug Administration (FDA) has authorized the use of several ICIs in specific subpopulations of mCRC patients. Nevertheless, there remains a dearth of direct comparative RCTs evaluating various treatment options. Consequently, the most effective ICI therapeutic strategy for microsatellite-stable (MSS) subgroup and microsatellite instability (MSI) subgroup in the first- and second-line therapies remains undefined. To address this gap, the present study employs a Bayesian network meta-analysis to ascertain the most effective first- and second-line ICI therapeutic strategies.MethodsA comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, with the retrieval date ranging from the databases’ inception to August 20, 2024. A total of 875 studies were identified, and seven were ultimately included in the analysis after a screening process. A systematic review and network meta-analysis were conducted on the basis of the search results.ResultsThis comprehensive analysis, comprising seven RCTs, evaluated first-line and second-line immunotherapy regimens in 1,358 patients diagnosed with mCRC. The treatments under investigation consisted of five initial treatments, including three focusing on MSS patients and two on MSI patients, as well as two secondary immunotherapy regimens, both focusing on MSS patients. A total of 1051 individuals underwent first-line treatment, while 307 received second-line treatment. The application of ICIs proved to offer varying degrees clinical benefits when compared to standard-of-care therapy alone, both in two subgroups of the first and the second treatment phases. Of particular note is the performance of Nivolumab combination with ipilimumab, which demonstrated superior efficacy in improving progression-free survival (PFS) (HR=0.21; 95% CI, 0.13-0.34),. Moreover, the treatment demonstrated an optimal safety profile, with a relatively low risk of adverse events (OR = 0.33; 95% CI, 0.19–0.56), compared to other first-line treatment modalities for MSI subgroup. Regarding MSS subgroup, the improvement of PFS by Nivolumab plus standard-of-care (SOC) was relatively significant (HR = 0.74; 95% CI, 0.53-1.02). In the realm of second-line therapies for MSS subgroup, the administration of Atezolizumab plus SOC has proven to be an effective approach for prolonging PFS, exhibiting an HR of 0.66 (95% CI, 0.44–0.99). These findings underscore the clinical benefits and safety profiles of ICIs in the treatment of mCRC across various treatment lines.ConclusionsThe clinical application of ICIs in both first- and second-line treatment strategies for patients with mCRC yields substantial therapeutic benefits. A detailed assessment in this study indicates that first-line treatment with Nivolumab combination with ipilimumab may represent an efficacious and well-tolerated therapeutic approach for MSI subgroup. In terms of MSS subgroup in first-line therapy, Nivolumab plus SOC may be a relative superior choice. In the context of second-line therapy for MSS subgroup, it is evident that a combination of Atezolizumab and SOC represents a preferable option for enhancing PFS. Furthermore, it is noteworthy that other ICIs treatment regimens also exhibit great value in various aspects, with the potential to inform the development of future clinical treatment guidelines and provide a stronger rationale for the selection of ICIs in both first- and second-line therapeutic strategies for mCRC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024543400.

Management of acral lentiginous melanoma: current updates and future directions.

Acral lentiginous melanoma is a rare subtype of melanoma generally associated with poor outcomes, even when diagnosed at an early stage. The tumor genetic profile remains poorly understood, but it is known to have a suppressed immune environment compared to that of non-acral cutaneous melanomas, which limits therapy options. There is significant attention on the development of novel therapeutic approaches, although studies are limited due to disease rarity. For local disease, wide local excision remains the standard of care. Due to frequent under-staging on preoperative biopsy, wider margins and routine sentinel lymph node biopsy may be considered if morbidity would not be increased. For advanced disease, anti-PD1 monotherapy or combination therapy with anti-PD1 and anti-CTLA4 agents have been used as first-line treatment modalities. Anti-PD1 and anti-CTLA4 combination therapies have been shown to be particularly beneficial for patients with BRAF-mutant acral lentiginous melanoma. Other systemic combination regimens and targeted therapy options may be considered, although large studies with consistent results are lacking. Regional and intralesional therapies have shown promise for cutaneous melanomas, but studies generally have not reported results for specific histologic subtypes, especially for acral melanoma. Overall, the unique histologic and genetic characteristics of acral lentiginous melanoma make therapy options significantly more challenging. Furthermore, studies are limited, and data reporting has been inconsistent. However, more prospective studies are emerging, and alternative therapy pathways specific to acral lentiginous melanoma are being investigated. As further evidence is discovered, reliable treatment guidelines may be developed.

Drug co-administration in the tumor immune microenvironment of Hepatocellular carcinoma

The etiology and exact molecular mechanisms of primary hepatocellular carcinoma (HCC) remain unclear, and its incidence has continued to increase in recent years. Despite tremendous advances in systemic therapies such as molecularly targeted drugs, HCC has some of the worst prognoses owing to drug resistance, frequent recurrence, and metastasis. Hepatocellular carcinoma is a widespread disease and its progression is regulated by the immune system. Traditional Chinese medicine (TCM) has been gradually theorized and systematized to have a holistic regulatory role for use in the prevention and treatment of tumors. Although half of the patients with HCC receive systemic therapy, traditionally sorafenib or lenvatinib are used as first-line treatment modalities. TCM is also widely used in the treatment of HCC, and the same immune checkpoint inhibitors (ICIs) such as PD-L1 have also received much focus in the field of continuously changing cancer treatment. Owing to the high probability of resistance to specific drugs and unsatisfactory efficacy due to administration of chemotherapy in single doses, the combination of drugs is the newest therapeutic option for patients with tumors and has become increasingly prominent for treatment. In this article, the research progress on combination therapy in the immunology of HCC is reviewed and the unique advantages of synergistic anti-tumor therapy with combination drugs are highlighted to provide new solutions for the clinical treatment of tumors. Graphical abstract: http://links.lww.com/AHM/A65

Pediatric-Onset Chronic Inflammatory Demyelinating Polyneuropathy: A Multicenter Study

BackgroundTo evaluate the clinical features, demographic features, and treatment modalities of pediatric-onset chronic inflammatory demyelinating polyneuropathy (CIDP) in Turkey. MethodsThe clinical data of patients between January 2010 and December 2021 were reviewed retrospectively. The patients were evaluated according to the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society Guideline on the management of CIDP (2021). In addition, patients with typical CIDP were divided into two groups according to the first-line treatment modalities (group 1: IVIg only, group 2: IVIg + steroid). The patients were further divided into two separate groups based on their magnetic resonance imaging (MRI) characteristics. ResultsA total of 43 patients, 22 (51.2%) males and 21 (48.8%) females, were included in the study. There was a significant difference between pretreatment and post-treatment modified Rankin scale (mRS) scores (P < 0.05) of all patients. First-line treatments include intravenous immunoglobulin (IVIg) (n = 19, 44.2%), IVIg + steroids (n = 20, 46.5%), steroids (n = 1, 2.3%), IVIg + steroids + plasmapheresis (n = 1, 2.3%), and IVIg + plasmapheresis (n = 1, 2.3%). Alternative agent therapy consisted of azathioprine (n = 5), rituximab (n = 1), and azathioprine + mycophenolate mofetil + methotrexate (n = 1). There was no difference between the pretreatment and post-treatment mRS scores of groups 1 and 2 (P > 0.05); however, a significant decrease was found in the mRS scores of both groups with treatment (P < 0.05). The patients with abnormal MRI had significantly higher pretreatment mRS scores compared with the group with normal MRI (P < 0.05). ConclusionsThis multicenter study demonstrated that first-line immunotherapy modalities (IVIg vs IVIg + steroids) had equal efficacy for the treatment of patients with CIDP. We also determined that MRI features might be associated with profound clinical features, but did not affect treatment response.

Education and Empowering Special Forces to Eradicate Secret Defectors: Immune System-Based Treatment Approaches for Mature T- and NK-Cell Malignancies.

Mature T- and NK-cell leukemia/lymphoma (MTCL/L) constitute a heterogeneous group of, currently, 30 distinct neoplastic entities that are overall rare, and all present with a challenging molecular markup. Thus, so far, the use of first-line cancer treatment modalities, including chemotherapies, achieve only limited clinical responses associated with discouraging prognoses. Recently, cancer immunotherapy has evolved rapidly, allowing us to help patients with, e.g., solid tumors and also relapsed/refractory B-cell malignancies to achieve durable clinical responses. In this review, we systematically unveiled the distinct immunotherapeutic approaches available, emphasizing the special impediments faced when trying to employ immune system defense mechanisms to target 'one of their own-gone mad'. We summarized the preclinical and clinical efforts made to employ the various platforms of cancer immunotherapies including antibody-drug conjugates, monoclonal as well as bispecific antibodies, immune-checkpoint blockades, and CAR T cell therapies. We emphasized the challenges to, but also the goals of, what needs to be done to achieve similar successes as seen for B-cell entities.

Risk of skin cancers in mycosis fungoides patients receiving PUVA therapy: A real-life experience from a single tertiary center.

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Skin-directed therapies, including phototherapy, are the first-line treatment modalities. Psoralen plus ultraviolet A light photochemotherapy (PUVA) is quite effective in controlling the disease; however, long-term adverse effects, particularly carcinogenesis, are the cons of this treatment. There are various studies on the negative impact of PUVA on skin cancer in patients with autoimmune skin diseases. The data on the long-term effects of phototherapy on MF patients are scarce. All MF cases that received PUVA alone or combined with other treatments at a single tertiary center were analyzed. This study compared the development of non-melanoma skin cancers, melanoma, and solid organ tumors in MF patients with at least 5-year follow-up data with age- and sex-matched controls. A total of 104 patients were included in the study. Ninety-two malignancies were detected in 16 (15.4%) patients, and six developed multiple malignancies. Skin cancers consisted of 56 basal cell carcinomas, 16 Bowen's disease, four squamous cell carcinomas, three melanomas, two basosquamous cell carcinomas, one Kaposi sarcoma, and one keratoacanthoma were found in nine (8.7%) patients. Eight patients developed three solid cancers and six lymphomas. The risk of developing skin cancer was associated with the total number of PUVA sessions (<250 vs ≥250 sessions; hazard ratio (HR) 4.44, 95% confidence interval (CI) 1.033-19.068; p = .045). 9 (13.2%) of 68 patients who had follow-ups for at least 5 years developed skin cancer. Compared to an age- and sex-matched cohort, the prevalence of new skin cancer was considerably greater (p = .009). Patients with MF are predisposed to develop secondary malignancies, and continual exposure to PUVA may potentiate this risk. Annual digital dermoscopic follow-up in MF patients treated with UVA is advised for early diagnosis and treatment of secondary cutaneous malignancies.

Use of the Scissor-Type Knife During the Peroral Endoscopy Myotomy Procedure for the Treatment of Achalasia

Peroral endoscopic myotomy (POEM) is one of the first-line treatment modalities along with pneumatic dilation and Heller myotomy for patients with achalasia. Endoscopists, especially trainees during the learning phase, commonly face difficulty in tissue plane dissection and selective myotomy while working near the esophagogastric junction, with increased risks of inadvertent injury, unexpected bleeding, and inadequate myotomy. To minimize the technical difficulty and improve the safety of POEM, we describe a protocol for using a scissor-type knife for the main steps of POEM, including mucosal incision, submucosal tunneling, myotomy, and hemostasis. The standard techniques used with the scissor-type knife involve grasping the target tissue, and then dissection or coagulation. The confirmation of the cutting line after grasping improves the accuracy and reliability of dissection, which is particularly useful for the selective myotomy of the internal circular muscle. Meanwhile, the scissor-type knife provides enhanced hemostatic capability and enables hemostasis and pre-coagulation without the device exchange for hemostatic forceps. Evaluation of the clinical outcomes in three patients who successfully received POEM using the scissor-type knife revealed no perioperative adverse events. At the 3-month follow-up, all patients achieved clinical success with postoperative Eckardt scores ranging from 0 to 1. In conclusion, the use of a scissor-type knife could minimize the technical difficulty and improve the safety of the POEM procedures, which may be suitable for trainees during the learning phase.

Use of the Scissor-Type Knife During the Peroral Endoscopy Myotomy Procedure for the Treatment of Achalasia

Peroral endoscopic myotomy (POEM) is one of the first-line treatment modalities along with pneumatic dilation and Heller myotomy for patients with achalasia. Endoscopists, especially trainees during the learning phase, commonly face difficulty in tissue plane dissection and selective myotomy while working near the esophagogastric junction, with increased risks of inadvertent injury, unexpected bleeding, and inadequate myotomy. To minimize the technical difficulty and improve the safety of POEM, we describe a protocol for using a scissor-type knife for the main steps of POEM, including mucosal incision, submucosal tunneling, myotomy, and hemostasis. The standard techniques used with the scissor-type knife involve grasping the target tissue, and then dissection or coagulation. The confirmation of the cutting line after grasping improves the accuracy and reliability of dissection, which is particularly useful for the selective myotomy of the internal circular muscle. Meanwhile, the scissor-type knife provides enhanced hemostatic capability and enables hemostasis and pre-coagulation without the device exchange for hemostatic forceps. Evaluation of the clinical outcomes in three patients who successfully received POEM using the scissor-type knife revealed no perioperative adverse events. At the 3-month follow-up, all patients achieved clinical success with postoperative Eckardt scores ranging from 0 to 1. In conclusion, the use of a scissor-type knife could minimize the technical difficulty and improve the safety of the POEM procedures, which may be suitable for trainees during the learning phase.

Erektil disfonksiyon 2.basamak tedavide intrakavernozal alprostadil kullanımının cinsel fonksiyonlar üzerine etkisi

Objective: In patients treated through the application of intracavernosal alprostadil in second-line treatment due to erectile dysfunction, the effect of the treatment on sexual functions measured with a 15-question International Index of Erectile Function (IIEF-15) questionnaire was investigated in this study. Material and Methods: Twenty-one patients treated due to erectile dysfunction between June 2018-October 2019, taking inadequate response from first-line treatment modalities, were applied intracavernosal alprostadil in second-line treatment and continued it for more than 12 weeks were included in the study, retrospectively. Ages, comorbid diseases, drug usage duration, drug-related side effects, penile Doppler ultrasonography (USG) parameters before application and the erection functions before and 12 weeks after drug use were evaluated with IIEF-15 form for the patients. Intracavernosal alprostadil was started with a dose of 5 μg and was continued with a dose of 10 μg as the result of dose titration. Results: The mean peak systolic blood flow velocity (PS) value of the patients was 24.4 ±15.1 cm/sec, and the mean end-diastolic flow velocity (ED) value was measured as 4.3±4.5 cm/sec based on the pre-treatment penile Doppler USG.Although the IIEF scores were measured in the 12th week, mean drug usage durations were measured as 21.9±16.6 weeks. Erectile Function Score was 9.2±5.3 before application; it was detected as 20.33±6.2 after the application. Orgasmic Function Score was 3.2±2.5 before application; it was detected as 7.5±2.4 after the application. Sexual Desire Score was 3.72±1.48 before application; it was detected as 8.9±1.4 after the application. Intercourse Satisfaction Score was 3.7±2.8 before application; it was detected as 9.1±2.7 after the application. Overall Satisfaction Score was 4±1.7 before application; it was detected as 8.1±1.7 after the application (All parameters p&lt;0.001). Conclusion: Intracavernosal alprostadil treatment used in erectile dysfunction second-line treatment is a cost-effective and efficient treatment method with a tolerable side effect profile and provides recovery in sexual parameters that can be measured with IIEF-15 parameters. Keywords: Alprostadil, erectile dysfunction, intracavernosal treatment.

The objective evaluation of triamcinolone acetonide efficacy in keloids management using Antera3D® imaging system.

Keloids are pathological scars characterized by nodular fibrous tissue that extends beyond the border of initial damage. These lesions do not spontaneously regress and can cause cosmetic disfigurements and functional disabilities. IntraLesional Injection of Triamcinolone Acetonide (ILITA), alone or in combination with other therapy, is one of the first-line treatment modalities. In this study the authors evaluated the objective efficacy of ILITA treatment in keloids management using this new imaging system. 37 patients with 45 keloid scars were treated with intralesional injection of triamcinolone acetonide (TAC) 20 mg/ml at an interval of three weeks. Antera3D® camera took the images and dates of the treated area in each patient, before the treatment (T0) and at three weeks after the last injection (T1). The system processed the levels of color, elevations, melanin and hemoglobin expression. All the scars were also evaluated, at the same times, by validated Vancouver Scar Scale (VSS). Comparison of the variables was performed using a Wilcoxon signed-rank test with a p < 0.05. At T0, mean VSS score was 8.67 ± 1.35 which reduced to 3.62 ± 1.72 at final follow up. Antera3D® scores were statistically significant differences in color (8.14 ± 2.41 vs 9.54 ± 1.81), protrusion (381.3 ± 15.6 vs 198.6 ± 21.3), melanin (0.53 ± 0.02 vs 0.62 ± 0.2) and hemoglobin (1.26 ± 0.41 vs 2.21 ± 0.41) expression levels after the treatment. In our clinical trial, the data results demonstrated that ILITA seems to be effective in reducing keloid dimensions and symptoms such as itching and pain, even if the treatment has local minimal adverse effects such as pain, telangiectasias and atrophy. Keloids are pathological scars characterized by nodular fibrous tissue that extends beyond the border of initial damage. Large keloids can cause cosmetic disfigurements and functional disabilities that affect quality of life. In literature, several treatment approaches have been described but, to date, no single method is considered superior. The International Advisory Panel on Scar Management recommended the use of intralesional steroid injections for keloids treatment. The efficacy of treatment may be evaluated with subjective scale; as no one can guarantee an objective evaluation. To eliminate the observer and/or patient factors, and to obtain a reliable, consistent, feasible, valid and objective evaluation a skin analysis camera system called Antera3D® (Miravex, Dublin, Ireland) can be used.In this study the authors evaluated the objective efficacy of triamcinolone acetonide treatment in keloids management using this imaging system. In this series, for Antera3D® scores there were statistically significant differences in color, protrusion, melanin and hemoglobin expression levels before and after treatment. The device directly shows the treatment changes, measured objectively and accurately, without bias of traditional evaluation scoring scale.Antera3D® system guarantees an objective evaluation of effectiveness of scar treatment enabling clinicians to modulate the therapy according to the scores registered.

Prevalence of post-prostatectomy erectile dysfunction and a review of the recommended therapeutic modalities.

Radical prostatectomy (RP) represents one of the most commonly used first-line treatment modalities in men with localized prostate cancer. One of the most feared post-surgical complications is erectile dysfunction (ED), usually caused by direct damage to the cavernous nerves or due to neuropraxia. Penile rehabilitation is an emerging concept that was proposed to stimulate and accelerate recovery of erectile function after RP. The goal is to improve blood flow to the penis, increasing cavernous oxygenation and avoiding fibrosis. The most common used modalities include oral phosphodiesterase type 5 inhibitors (PDE5-I), vacuum erection devices (VEDs), intracorporeal injection (ICI) therapy, medicated urethral system for erections (MUSE), and a combination of these treatments. For those patients with severe ED, ED refractory to medical therapy and/or seeking long term reliable results, the penile prosthesis implant remains an excellent alternative. We conducted a broad review of post-prostatectomy ED prevalence with different techniques and the success rates of the different therapeutic approaches.

P14.99 Clinical and biologic features predictive of survival after relapse of childhood medulloblastoma

Abstract BACKGROUND Salvage therapy for recurrent medulloblastoma (MB) is not standardized. Factors associated with survival after recurrence have not been reported. MATERIAL AND METHODS Medical records were reviewed for 155 consecutive patients with newly diagnosed MB between 2007 and 2017, treated at Gustave Roussy and Hospital Necker. The following variables were collected for all patients: age at diagnosis, stage, histology (central review according to WHO 2016 classification), molecular subgrouping (DNA methylation), first-line treatment modalities, time to relapse, pattern of recurrence and current status. RESULTS A disease recurrence was observed in 47 patients (30%) at a median time of 15 months (range, 1–88 months). The 1-year survival after recurrence was 44% (CI 95%,29.6 to 58.8). The pattern of recurrence was local in 9 patients, metastatic in 21 and combined local and metastatic in 17 patients. The time to first recurrence, less or more than 12 months from diagnosis, was a predictor of post-recurrence overall survival (p &lt; 0.0001) after adjustment for age, treatment, MYC amplification and molecular subgroups. Twenty-seven patients (57%) experiencing recurrent or progressive disease more than 12 months after diagnosis, had an estimated 1-year survival after recurrence of 100% (CI 95%, 100.0 to 100.0) vs 30% (CI 95%, 12.2 to 50.1) with an earlier recurrence. Early relapse was more frequent in children younger than 5 years of age at diagnosis (75% vs 37%, p =0.009), anaplastic/large cell MB (30% vs 3.7%, p=0.046) and Group 3 tumours (76.5% vs 20.8%, p=0.003). Other factors influencing post-relapse survival were metastatic disease and treatment modalities at diagnosis. Multivariable analyses will be presented. CONCLUSION The overall prognosis after relapse remains poor. Time to relapse is a significant prognostic factor for postrelapse survival and may help in the design of clinical trials evaluating new agents.

Radical prostatectomy and simultaneous penile prosthesis implantation: a narrative review.

Radical prostatectomy (RP) represents one of the most commonly used first-line treatment modalities in men with localized prostate cancer (PCa). Despite efforts to preserve the neurovascular bundles with nerve sparing (NS) surgery, erectile dysfunction (ED) remains common after RP and this may significantly affect patients' quality of life (QoL). The aim of this paper is to evaluate the outcome of simultaneous placement of penile prosthesis and RP. The ideal candidates for simultaneous penile prosthesis implantation are those who report pre-existent refractory ED and patients in whom there is a high risk of extracapsular disease, such as any cT2c or cT3, and undergo non-nerve sparing RP. If the patient chooses to undergo PPI to treat his refractory ED it is clear that this procedure will be associated with higher patients' satisfaction rates, if carried out simultaneously with RP rather than at a later stage. A simultaneous procedure would avoid two admissions, reduce hospitalization time and guarantee a faster recovery of sexual function, preventing the otherwise unavoidable loss of penile length. Since the urologist does not need to preserve the neurovascular bundles, as the penile implant will take care of postoperative rigidity, RP can be performed more radically from an oncological point of view, thus reducing the risk of recurrence and metastasis, especially in patients with high risk of locally advanced disease. In conclusion, simultaneous PPI with RP provides early sexual rehabilitation, improving patients' quality of life, without compromising surgical outcomes. However, larger series will be necessary, to better identify the patients who are more likely to benefit from nerve sparing surgery and postoperative penile rehabilitation from those who would are more likely to develop refractory ED post RP and would therefore benefit from simultaneous implantation of a penile prosthesis.

Treatment Modalities and Survival in Older Adults with Metastatic Colorectal Cancer in Real Life.

Metastatic colorectal cancer (mCRC) is increasingly treated with targeted therapies, but little is known about real-life mCRC treatment in older adults. The aims were to describe the real-life first-line treatment modalities in older adult mCRC patients, to identify factors associated with treatment modalities, and to evaluate survival with regard to treatment modalities. A cohort of mCRC patients aged 65 years and older at diagnosis was identified between 2009 and 2013 using French national healthcare insurance system claims data. Treatment modalities were: treatment with one or more anticancer medication vs best supportive care and, among treated patients, treatment with targeted therapy vs conventional chemotherapy alone. Multivariate logistic regression was used to identify factors associated with treatment by anticancer medication and by targeted therapy. Cox proportional hazards models were used to assess the independent effect of treatment modalities on overall survival while adjusting for baseline covariates identified with logistic regression. A total of 503 patients were included with a median age of 78 years (54% were men). Of these, 299 (59%) were treated with anticancer medications. Among treated patients, 131 (44%) received targeted therapy. In multivariate analysis, age 75 years or older, renal failure, malnutrition, and five or more concomitant medications were associated with a lower likelihood of treatment with anticancer medications. Among treated patients, age 75 years or older, history of cancer, lymph node metastases, and a single metastatic site were associated with a lower likelihood of treatment with targeted therapy. Multivariate Cox proportional hazards models found that treatment with any anticancer medication tended to be associated with a lower risk of death; treatment with targeted therapy was not significantly associated. A more appropriate prescription of anticancer medications in the older adult will require the definition of more explicit criteria to avoid undertreatment. The real benefit of targeted therapies vs conventional chemotherapy alone needs to be confirmed in this population. J Am Geriatr Soc 67:913-919, 2019.

A Review of Hepatocellular Carcinoma in Elderly Patients Focused on Management and Outcomes.

Recent studies report a significant age-specific increase in hepatocellular carcinoma (HCC) development among persons over 75 years old. Therefore, there is an urgent need to determine the optimal treatment strategy in elderly patients with HCC. This systemic review examines the clinical characteristics, efficacy, and safety of first-line treatment modalities. The literature was searched regarding epidemiology and clinical outcomes in elderly patients (age ≥75 years) undergoing first-line treatment for HCC. Causative or comorbid conditions of HCC in elderly patients differed from those in younger patients. Radiofrequency ablation may be effective and safe in early stages. Surgical resection may also be feasible in the early stages for selected patients. Transarterial chemoembolization may be safe and effective for intermediate HCC, and sorafenib may be feasible in elderly patients with advanced HCC. Prospective randomized trials are needed to establish the treatment strategy for elderly patients with HCC.

Prognostic Impact of Gastrointestinal Involvement in Newly Diagnosed Diffuse Large B-Cell Lymphoma

Introduction: Involvement of >1 extranodal site is regarded as a poor prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). It is necessary to clarify the prognostic impact of specific extranodal sites. Gastrointestinal (GI) involvement is one of the most frequently involved extranodal sites.Methods: Patients with newly diagnosed DLBCL treated at the University of Heidelberg between 06/2001 and 07/2015 were identified and included in this retrospective analysis. Data on clinical characteristics and treatment modalities were obtained by review of medical charts. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The impact of variables on PFS and OS was evaluated by univariate log-rank tests and by multivariate analysis using the Cox proportional hazards model.Results: A total of 1001 patients were identified of whom 119 (11.9%) presented with GI involvement. Median age of patients with GI involvement was 63.3 years [range 19.1-86.7], 71 (59.7%) were male. 92 patients had an available international prognostic index (IPI) score, 36 (39.1%) IPI 0-1, 33 (35.9%) IPI 2-3, and 23 (25%) IPI 4-5. The most frequently involved organs of GI were stomach (51.3%), small intestine (39.5%), colon (20.2%), and esophagus (2.5%).107 (89.9%) patients were treated in curative intent and were further analyzed regarding the prognostic impact of several factors on outcome. 80.4% of them received CHOP-like therapies, 17.8% received chemotherapy more aggressive than CHOP, typically addition of etoposide or treatment with high-dose methotrexate in case of CNS involvement, 87.9% received additional rituximab, and 22.4% additional radiotherapyIn DLBCL patients with GI involvement, we identified factors associated with worse OS (P<.05) by univariate analysis: B symptoms, elevated serum LDH, and involvement of more than two extranodal sites. On the contrary, age (>60 years), sex, Ann Arbor Stage (AAS) III/IV, and Performance Status of Eastern Cooperative Oncology Group(ECOG) more than one, and elevated serum sCD25 did not have any significant impact on OS. B symptoms were as well associated with decreased PFS (P<.05) by univariate analysis.Multivariate Cox Regression analysis revealed that patients with elevated serum LDH at diagnosis had significantly worse OS (P<.05), and patients with B symptoms had significantly worse PFS (P<.05).Regarding first-line treatment modalities, escalation of chemotherapy to more aggressive regimes than CHOP was associated with a prolonged OS and PFS in univariate analysis, not in multivariate analysis. Radiotherapy did not have any significant impact on OS or PFS.Regarding all DLBCL patients treated with curative intent, GI involvement did not have any significant prognostic impact on OS or PFS.Conclusions: In this retrospective registry analysis of patients with newly diagnosed DLBCL with GI involvement, B symptoms, elevated serum LDH, and involvement of more than two extranodal sites were identified as risk factors for inferior OS. Escalation of chemotherapy to more aggressive regimes than CHOP was associated with a prolonged OS and PFS.Further analyses are required as toward which treatment modalities might be best suited to improve prognosis of GI involvement. DisclosuresKriegsmann:Celgene: Research Funding; BMS: Research Funding.

29] Time of onset of symptom relief after intraoperative detrusor injection of botulinum toxin A in patients with neurogenic and non-neurogenic overactive bladder syndrome

ObjectiveTo investigate the controversy that still exists regarding the time of onset of symptom relief after intraoperative detrusor injection of botulinum toxin A (BOTOX) in patients with neurogenic and non-neurogenic overactive bladder syndrome (OAB), as intra-detrusor injection of botulinum toxin has emerged as a second-line option for patients with neurogenic and non-neurogenic OAB who are refractory to first-line treatment modalities.

Retrospective Evaluation of Hairy Cell Leukemia Patients Treated with Three Different First-Line Treatment Modalities in the Last Two Decades: A Single-Center Experience.

Objective:In this study, we retrospectively analyzed the clinical outcome, treatment responses, infectious complications, and survival rates of 71 hairy cell leukemia (HCL) cases.Materials and Methods:Sixty-seven patients received a first-line treatment and 2-chlorodeoxyadenosine (cladribine-2-CdA) was administered in 31 cases, 19 patients received interferon-alpha (INF-α), splenectomy was performed in 16 cases, and rituximab was used in one.Results:Although the highest overall response rate (ORR) was observed in patients receiving 2-CdA upfront, ORRs were comparable in the 2-CdA, INF-α, and splenectomy subgroups. Relapse rates were significantly lower in patients who received first-line 2-CdA. The progression-free survival (PFS) rate with 2-CdA was significantly higher than in patients with INF-α and splenectomy, but we found similar overall survival rates with all three upfront treatment modalities. Infections including tuberculosis were a major problem.Conclusion:Although purine analogues have improved the ORRs and PFS, there is still much progress to make with regard to overall survival and relapsed/refractory disease in patients with HCL.

Retrospective evaluation of hairy cell leukemia patients treated with 3 different first-line treatment modalities in the last two decades: a single center experience

Retrospective evaluation of hairy cell leukemia patients treated with 3 different first-line treatment modalities in the last two decades: a single center experience

Barcelona clinic liver cancer-stage C hepatocellular carcinoma: A novel approach to subclassification and treatment.

Barcelona clinic liver cancer-stage C (BCLC-C) encompasses a broad spectrum of tumor burdens, liver function statuses, patient prognoses, and treatment strategies. Currently, sorafenib is the only recommended treatment for patients with BCLC-C and outcomes remain suboptimal. The aims of this study were to assess the heterogeneity of BCLC-C hepatocellular carcinoma (HCC) cases, propose a novel subclassification for these cases, and suggest optimal treatment strategies other than sorafenib.We retrospectively analyzed 196 consecutive BCLC-C HCC patients who were diagnosed and treated between January 2008 and December 2015.All 196 patients were classified according to the modified Union for International Cancer Control (Stage I, 0.0%; Stage II, 8.2%; Stage III, 64.3%; Stage IVA, 21.9%; and Stage IVB, 5.6%) and American Joint Committee on Cancer TNM staging systems (Stage I, 0.0%; Stage II, 16.3%; Stage IIIA, 27.6%; Stage IIIB, 49.5%; Stage IIIC, 1.5%; Stage IVA, 1.0%; and Stage IVB, 4.1%). First-line treatment modalities included surgical resection (8.7%), transarterial chemoembolization (49.5%), hepatic arterial infusion therapy (5.6%), sorafenib therapy (9.2%), radiotherapy (9.2%), and best supportive care (10.7%). In univariate analysis, Child-Pugh score, tumor size, distant metastasis, multinodular or infiltrative/diffuse type of HCC, main portal vein invasion, hepatic vein invasion, and bile duct invasion were significantly associated with survival (P < .001). Tumor size, distant metastasis, HCC type, and bile duct invasion remained significantly associated with 1-, 3-, and 5-year survival rates in multivariate Cox regression analyses. Using these 4 characteristics, a novel subclassification of BCLC-C was developed and applied to the patient cohort. The subclassification included 5 substages (stages C0–C4), as defined based on the number of characteristics that were present in each HCC case (0–4). The subclassification showed significant associations with survival, with median survival times of 3026 days, 605 days, 224 days, 126 days, and 82 days for patients with Stage C0, C1, C2, C3, and C4 disease, respectively (P < .001). Additionally, diverse survival rates were observed when different treatment modalities were selected for cases within each substage.The proposed BCLC-C subclassification of HCC patients is effective in providing better prognostic subclassifications and more appropriate treatment strategies.