Patients Undergoing Induction Therapy Research Articles

Ocular manifestations of acute myeloid leukemia during induction phase of chemotherapy: A case series

The aim of this series is to report diverse ocular features noted in patients during the induction phase in acute myeloid leukemia (AML). Three female patients undergoing induction therapy for AML reporting for various ocular complaints were examined. Detailed history, including the onset of AML and chemotherapy and any past ocular or systemic ailment, was taken. Best-corrected visual acuity, anterior segment, and posterior segment examinations were performed. Intraocular pressure was measured, and color vision was tested. Routine hematological, and biochemical investigations and imaging were done when required. Patients with abnormal parameters were referred to an oncologist for management. A varied spectrum of ocular manifestations was noted in these three female patients, including preseptal cellulitis, orbital cellulitis, and subhyaloid hemorrhages. Immediate treatment was given to patients with vision-threatening conditions in consultation with an oncologist and otorhinolaryngologist, and patients responded well to the treatment. Owing to its cytoreductive action, AML induction therapy exposes the patient to various adverse events, causing significant ocular and systemic morbidity. All the diagnosed patients of AML are recommended to undergo a baseline ocular assessment.

Use of CLL1 and CD45RA As Biomarkers for Leukemia Stem Cells in Acute Myeloid Leukemia Re-Induction Therapy Decision Making

Background: The decision to re-induce patients with newly diagnosed acute myeloid leukemia (AML) currently relies on morphological evaluation of leukemia blasts in post treatment bone marrow, with more than 5% bone marrow blast counts indicating necessity of re-induction therapy. Our previous study showed that changes in Leukemia Stem Cell (LSC) subsets, identified by CLL1 (CD371) or CD45RA as specific markers, are highly correlated with therapeutic outcome. In this study, we focus on newly diagnosed AML patients undergoing induction therapy to determine whether information gained from LSC subset analysis can aid in decision making for re-induction therapy. Methods: We analyzed flow cytometry data from bone marrow aspirate in patients with newly diagnosed AML of all types except acute promyelocytic leukemia (M3) before and after induction therapy from a single institution. “Leukemic blasts” were identified by morphology and leukemia-associated immunophenotype by Multicolor Flow cytometry (MFC). Hematopoietic stem cells (HSCs) gating was based on CD45 dim/SSC and CD34 +CD38 low/- expression. Leukemic stem cells (LSC) subset was analyzed using % of CD371 (CLL-1) or CD45RA positive cells over total HSCs (%CLL1 +/CD34 +CD38 - or %CD45RA +/CD34 +CD38 -). Newly diagnosed AML with >50% (CLL1 +/CD34 +CD38 - or CD45RA +/CD34 +CD38 -) on diagnosis was selected for further study. Fold change of LSC subset was calculated using LSC percentage post-induction divided by LSC percentage on diagnosis. Chart review was conducted to determine correlation between LSC subset change, bone marrow blasts count and clinical course. Mann-Whitney test was used for statistical analysis. Results: Forty-eight newly diagnosed AML (non-M3) cases, who received at least one cycle of induction therapy with both pre- and post-treatment bone marrow biopsy were reviewed. Twenty-seven cases were identified with CLL1 +/CD34 +CD38 - or CD45RA +/CD34 +CD38 - above the 50% threshold on diagnosis. Four cases were later excluded due to inadequate CD34 +CD38 - cellular events on flow cytometry (<20) in post-treatment bone marrow samples. As shown in figure 1, in all the 9 patients with post induction blasts counts of less than 5% (complete remission, CR), post induction LSC subset is reduced to less than 0.5× of LSC subset on diagnosis. Thus, post induction LSC subset less than 0.5× of diagnosis is used as cut off for “adequate reduction”. In 14 patients with residual blasts of more than 5%, there is a wide range of LSC subset change. Interestingly, 6 of them showed adequate reduction of LSC subsets, similar to patients who achieved CR. Among them, one was observed and showed CR on repeat bone marrow biopsy at a later time point without further therapy. The other 5 patients were given re-induction and achieved CR after a second cycle. Eight patients with residual blasts did not achieve adequate reduction of LSC subset (residual LSC subset > 0.5× of diagnosis). Five achieved CR on subsequent re-induction. Three had persistent disease and failed to achieve CR despite 3 cycles of induction therapy. Conclusion: In newly diagnosed AML with high percent of CLL1 +/CD34 +CD38 - or CD45RA +/CD34 +CD38 - LSC subset on diagnosis, monitoring LSC subset offers additional information regarding efficacy of induction therapy. All the patients with CR showed residual LSC subset of 0.5-fold or less compared to LSC subset on diagnosis (defined as “adequate reduction” of LSC subset). For patients who did not achieve remission but adequately reduced LSC subset, which indicates efficacy of induction therapy, observation with repeat bone marrow biopsy, or re-induction with similar regimen can be considered. For patients with no adequate reduction of LSC subset, intensified chemotherapy or alternative therapy with different mechanism of action needs to be considered to maximize the possibility of achieving CR on re-induction. A multi-institutional study with more patients is needed to confirm these findings and validate these LSC biomarkers for this important treatment decision making in AML.

Sebaceous carcinoma in solid organ transplant recipients: The elegant path from epidemiology to etiology

Sebaceous carcinoma (SC) is a rare skin cancer associated with rapid progression and relatively poor survival, particularly in solid organ transplant recipients (SOTRs). Immunosuppressive regimens place SOTRs at substantially increased risk of a variety of skin cancers; recent research has shown a 25-fold increase in SC in the SOTR population, especially among lung recipients, older males, those with longer time since transplant, and patients undergoing induction therapy with thymoglobulin. The potential etiologic mechanisms underlying SC are multifaceted and complex. Immunosuppression creates a microcosm through which to view causative factors for carcinogenesis which has implications in elucidating mechanistic etiologies for SC far beyond the SOTR population, since not all cancers are more common in immunosuppressed patients. Research integrating the role of oncogenic viruses, underlying medical conditions, genetic risk factors, toxicity of prophylactic medications, drug-induced photosensitization, and T-cell deficiency/dysfunction is needed to better elucidate the factors underlying SC in immunosuppressed hosts. In this report, we integrate current research regarding SC in SOTR patients using the causal pie/sufficient-component cause model. In doing so, we provide a paradigm through which to view future research regarding the etiology of SC.

Acute Myeloid Leukemia Place of Death: Change over Two Decades

Introduction: Acute Myeloid Leukemia (AML) outcomes have improved over time, however end-of-life care for patients with AML is suboptimal with a low utilization of palliative care and hospice services. We analyzed AML mortality cause from 2000 to 2019 using the Mortality Data from the Centers of Disease Control and Prevention (CDC). Among AML deaths, we evaluated differences in place of death, cause of death and sociodemographic characteristics including gender, race and resident status. Methods: We conducted a retrospective cohort study using the Multiple Cause of Death Mortality Data from the National Vital Statistics System of the National Center for Health Statistics from January 1st 2000 to December 31st 2019. We obtained demographic characteristics of all the deaths during this period and those with AML. Among AML deaths, we examined principal cause of death and then used joinpoint regression to calculate trends in the rates of AML deaths by their location, which was represented using average annual percentage change (AAPC). Results: 195,923 AML deaths were captured from 2000 to 2019, from more than 50 million total deaths during this timeframe. At least 85.3% of AML deaths were attributed to AML (index cancer) and 2.7% of deaths were attributed to infection. 56.0% of AML deaths occurred in hospitals, 24.7% in decedent's homes, 7.5% in hospice facilities and 8.3% in nursing homes or long term care facilities. 56.6% of AML deaths were in males. 83.1% of AML deaths were in Non-Hispanic Whites (NH-White), 7.7% in NH-Blacks and 5.8% in Hispanics. 68.8% of AML deaths were residents of state in which the death occurred and 30.9% were in non-residents. Over the studied period, there was a statistically significant decrease in AML deaths in the hospital setting with AAPC (95% CI) being -1.5 (-1.9,-1.1) and nursing home setting AAPC (95% CI): -2.5 (-4.8, -0.2) along with a statistically significant increase in AML deaths at home with AAPC (95% CI): 28.6 (15.0, 43.7) (Figure 1). The AAPC for deaths in hospice facilities was statistically non-significant. Conclusions: Most AML deaths continue to occur in the hospital setting despite a statistically significant increase in deaths at home and trend of increased utilization of hospice facilities. Patients undergoing induction therapy for new or relapsed disease may be at higher risk of death from complications from their disease or therapy and die in the hospital setting. Young age at diagnosis, delayed goals of care discussions and hesitancy to forego transfusions may contribute to increased AML deaths in the hospital setting. This is the largest population study to date evaluating AML deaths to our knowledge, however we are limited by lacking information on the risk stratification of the AML, treatment received and circumstances of home death. We are also unable to determine the timing of goals of care conversations, whether or not patients were offered palliative care services or the timing of the hospice referral when it did occur. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Thoracoscopic Versus Open Lobectomy After Induction Therapy for Nonsmall Cell Lung Cancer: New Study Results and Meta-analysis.

The use of video-assisted thoracoscopic surgery (VATS) lobectomy has become a mainstay of modern thoracic surgery practice and the technique of choice for resection of early-stage lung cancers. However, the benefits of VATS following induction therapy are yet to be clarified. This study aims to assess whether VATS lobectomy achieves similar perioperative and oncologic outcomes compared to thoracotomy for nonsmall cell lung cancer after induction therapy. We retrospectively reviewed the outcomes of 72 patients who underwent lung lobectomy after induction therapy in our institution from January 2017 to January 2020. Subsequently, we carried out a comprehensive literature search and pooled our results with available data from previously published studies to perform a meta-analysis. VATS was associated with reduced intraoperative blood loss (P=0.05) and less perioperative complications (P=0.04) in our local institution. The meta-analysis comprised nine studies. A total of 943 patients underwent VATS and 2827 patients underwent open lobectomy. VATS was associated with significant shorter surgery duration (P<0.0001), shorter chest-tube drainage duration (P<0.0001), and shorter hospital stays (P<0.0001). Furthermore, there was significantly less perioperative complications (P=0.006) and less intraoperative blood loss (P=0.036) in the VATS group. However, there were no significant differences in 3-y overall survival and 3-y disease-free survival rates. In some selected patients undergoing induction therapy, VATS lobectomy could achieve equivalent perioperative outcomes to thoracotomy but evidence is lacking on oncologic outcomes. Further trials with a focus on oncologic outcomes and longer follow-up are required.

Deep remission within 12 months prevents renal flare and damage accrual in lupus nephritis.

To evaluate the significance of achieving deep remission by induction therapy in lupus nephritis (LN) patients. We assessed consecutive patients undergoing induction therapy for active LN. Achievement of complete renal response (CR) was defined as a urine protein creatinine ratio (UPCR) ≤0.5 g/gCr, and deep remission (DR) was defined as a UPCR ≤0.15 g/gCr with stabilisation of serum creatinine levels assessed every 2-3 months. We compared renal flare and damage accrual rates among patients with CR, CR without DR, and DR at 3, 6, and 12 months and later. Fifty-nine Asian patients were enrolled, and the median observation period was 48.6 months. Of these, 55 patients achieved CR, and 33 achieved DR within 12 months of receiving induction therapy. The patients with DR within 12 months experienced a significantly lower rate of subsequent renal flare (p<0.001) and damage accrual (p=0.046) than those without CR, those with DR after 12 months, and those with no DR but CR within 12 months. In addition, younger age, shorter disease duration, lower urine protein at baseline, and earlier renal response were associated with DR within 12 months. Achievement of DR within 12 months after induction therapy should be a treatment target for active LN, as it has implications for preventing renal flare and damage accrual.

Baseline peripheral neuropathy was associated with age and a prognostic factor in newly diagnosed multiple myeloma patients

Multiple myeloma (MM) is an incurable plasma cell hematological malignancy. Bortezomib has become the primary drug in the treatment of patients with MM. However, its negative effects, especially peripheral neuropathy (PN), affect the patients’ life quality and treatment continuity. However, there are few studies on baseline PN of MM, and little is known of the impact of baseline PN on the prognosis of MM patients. Therefore, we reviewed the clinical data of newly diagnosed MM patients in our center, explored the influencing factors of baseline PN, and evaluated PN’s influence on the prognosis of MM patients undergoing induction therapy with bortezomib. According to the inclusion and exclusion criteria, 155 MM patients were eligible for the retrospective study. The multivariate regression analysis, generalized additive fitting smooth curve, the receiver operating characteristic curve (ROC) and K-M curve were conducted in this study. We found that baseline PN in patients with MM was age-related; MM patients with baseline PN have more severe bortezomib induced PN (BiPN) during the four courses of induction therapy with bortezomib as the primary regimen and worse PN outcome after induction therapy. Additionally, the progression-free survival (PFS) and overall survival (OS) of MM patients with baseline PN were worse than those of the MM patients without baseline PN.

Bone Marrow Soluble Immunological Mediators as Clinical Prognosis Biomarkers in B-Cell Acute Lymphoblastic Leukemia Patients Undergoing Induction Therapy.

Different factors are used as predictors of unfavorable clinical outcomes in B-Cell Acute Lymphoblastic Leukemia (B-ALL) patients. However, new prognostic markers are needed in order to allow treatment to be more accurate, providing better results and an improved quality of life. In the present study, we have characterized the profile of bone marrow soluble mediators as possible biomarkers for risk group stratification and minimal residual disease (MRD) detection during induction therapy. The study featured 47 newly-diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients that were categorized into subgroups during induction therapy according to risk stratification at day 15 [Low Risk (LR), Low Risk increasing to High Risk (LR→HR) and High Risk (HR)] and the MRD detection on day 35 (MRD(-) and MRD(+)). Soluble immunological mediators (CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-1β, IL-6, TNF, IFN-γ, IL-17A, IL-4, IL-5, IL-10 and IL-2) were quantified by cytometric bead array and ELISA. Our findings demonstrated that increased levels of CCL5, IFN-γ and IL-2 at baseline appeared as putative candidates of good prognosis in LR and MRD(-) subgroups, while CCL2 was identified as a consistent late biomarker associated with poor prognosis, which was observed on D35 in HR and MRD(+) subgroups. Furthermore, apparently controversial data regarding IL-17A and TNF did not allow the definition of these molecules as either positive or negative biomarkers. These results contribute to the search for novel prognostic indicators, and indicate the potential of bone marrow soluble mediators in prognosis and follow-up of B-ALL patients during induction therapy.

Acute Respiratory Distress Syndrome in a Patient With Acute Promyelocytic Leukemia: Overlapping Between Differentiation Syndrome and COVID-19

Differentiation syndrome (DS) is a relatively common and severe complication in acute promyelocytic leukemia (APL) patients undergoing induction therapy with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO). DS is a multisystem disorder with pulmonary involvement. The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is also a systemic disorder with similar pulmonary and other clinical manifestations as DS. Here, we report an APL case with overlapping between DS and COVID-19. After admission to the hospital, the patient was diagnosed with APL and underwent differentiation therapy with ATRA/ATO. In the meantime, COVID-19 was diagnosed with a positive polymerase chain reaction test of SARS-CoV-2 from an oropharyngeal swab. The patient developed acute respiratory distress syndrome, coagulopathy, and acute kidney injury, which fit the clinical pictures of both DS and COVID-19. The patient died at last and this complicate case imposed big challenges for clinicians due to the laboratory and imaging findings of DS disguised in the context of COVID-19. Therefore, comprehensive treatment strategy should be considered to balance the risk and benefit of differentiation therapy in the context of COVID-19.

Outcomes in Obese Patients Undergoing Induction Therapy for Acute Leukemia

Obesity continues to be a growing concern in the United States. According to the guidelines published by ASCO in 2012, chemotherapy doses in this patient population should be calculated based on actual body weight. However, the guidelines do not provide guidance for chemotherapy dosing in patients with hematologic malignancies. We conducted a single-center retrospective chart review (from November 2012 to August 2016) to evaluate clinical outcomes in obese versus nonobese patients undergoing induction chemotherapy for newly diagnosed acute leukemia. All chemotherapy doses were calculated based on actual body weight. The primary outcome was rate of complete remission (CR) following induction chemotherapy. Secondary outcomes included time to absolute neutrophil count (ANC) and platelet recovery, the incidence of febrile neutropenia and clinical or microbiological infections, rate of early (0-15 days) and in-hospital mortality, and overall survival at 6 months. The rate of CR was similar between obese patients and non-obese patients diagnosed with AML (60% vs 61.9%; p=0.86) and ALL (87.5% vs 92.8%; p=0.31). Obese patients with AML were more likely to receive re-induction chemotherapy following 14-day bone marrow biopsy (53.3% vs 23.2%; p=0.019). There were no significant differences in secondary outcomes in either group when comparing obese versus non-obese patients. Obese patients with acute leukemia had similar rates of CR compared to non-obese patients following induction chemotherapy. While chemotherapy dosing based on actual body weight did not lead to excessive toxicity in these patients, continued research is needed to determine optimal dosing and long-term outcomes in this patient population. DisclosuresNo relevant conflicts of interest to declare.

Neoadjuvant chemoradiation followed by transanal local excision for T2 rectal cancer confers equivalent survival benefit as traditional transabdominal resection

BackgroundDespite clinical guidelines classifying T2 rectal cancer as a contraindication for transanal local excision attributable to unacceptably high rates of local recurrence, it is a practice that persists clinically. Recent clinical trials have suggested that transanal local excision in addition to neoadjuvant chemoradiation is an acceptable alternative in select patients. MethodsThe 2004–2015 National Cancer Database was queried for patients with clinical stage T2N0M0 rectal adenocarcinoma who underwent surgical intervention. Patients were stratified by treatment with transabdominal resection or transanal local excision, both with and without neoadjuvant chemoradiation. Propensity matching was performed, and, using the Kaplan-Meier and Cox proportional hazard models, survival was compared between the groups. ResultsA total of 12,021 patients met inclusion criteria, including 1,761 and 6,629 patients who underwent transabdominal resection with and without neoadjuvant chemoradiation, respectively, and 695 and 2,936 patients who underwent local transanal excision with and without neoadjuvant chemoradiation, respectively. In unadjusted analysis, patients undergoing induction therapy followed by transabdominal resection or local excision had equivalent survival. Similarly, on multivariate Cox proportional hazard regression after propensity matching, local excision was not an independent predictor of patient mortality compared with transabdominal resection (hazard ratio 0.93, 95% confidence interval 0.75–1.16). ConclusionLocal transanal excision in addition to neoadjuvant chemoradiation may provide comparable survival benefit to transabdominal resection for patients with clinical stage T2N0M0 rectal cancer. Therefore, patients who refuse or are poor candidates for transabdominal resection should be considered for neoadjuvant therapy followed by transanal local excision.

Consensus in Identification and Stability of Symptom Clusters Using Different Symptom Dimensions in Newly Diagnosed Acute Myeloid Leukemia Patients Undergoing Induction Therapy

ContextAn unresolved issue in symptom cluster (SC) research is that the numbers and types of SCs vary based on the multiple dimensions of the experienced symptoms that are used for SC identification. ObjectiveThis study aimed to identify SCs using the ratings of occurrence, severity, and distress in newly diagnosed acute myeloid leukemia (AML) patients at three stages of their induction therapy (i.e., T1, T2, and T3). Then, we evaluated the consensus among the numbers and types of symptoms in each SC identified by multiple dimensions over time. MethodThe Chinese version of the Memorial Symptom Assessment Scale was used to evaluate the occurrence, severity, and distress ratings of 32 symptoms in patients newly diagnosed with AML during their induction therapy. Exploratory factor analysis was used for SCs identification. ResultsUsing the three dimensions in the AML patients (n = 126), four SCs were identified at T1 and T3 and three SCs were identified at T2. The number of symptoms in individual SCs varied over time, whereas the specific symptoms in SCs remained similar over time. The severity ratings fit the data better than did the ratings of occurrence and distress. ConclusionThese findings provided insights into the most common SCs in AML patients undergoing induction therapy by multidimensional evaluation and could lay the foundation for future targeted symptom interventions. Further studies are needed to explore the mechanisms of SCs in AML patients undergoing the chemotherapy.

Pneumonectomy in Stage IIIA-N2 NSCLC: Should It Be Considered After Neoadjuvant Chemotherapy?

BackgroundOwing to the expected poor long-term outcomes and high postoperative morbidity and mortality, patients with stage IIIA-N2 tumors candidate to pneumonectomy (PN) are usually excluded from surgery. This study aims to analyze the outcome of patients who underwent PN to prove its safety and feasibility. Patients and MethodsWe retrospectively analyzed data from 233 patients who underwent PN for N2 non–small-cell lung cancer (NSCLC) between 1998 and 2015. Eighty-five patients were occult N2 disease (group 1), whereas 148 patients underwent induction therapy (IT) for stage IIIA-N2 (group 2). ResultsOverall morbidity, postoperative mortality, and 90-day mortality rates were 46.8%, 2.6%, and 8.6%, respectively. The 2 groups (group 1 vs. 2) had similar postoperative and 90-day mortality rates: 2.4% versus 2.7% (P = 1.00), and 9.4% versus 8.1% (P = .81), respectively. The incidence of major morbidity was higher and statistically significant in group 2 compared with group 1: 23% versus 12.9% (P = .1). Postoperative bronchopleural fistula occurred in 4.7% (4/85) of patients with occult N2 (group 1) and in 10.1% (15/148) of patients undergoing IT (group 2) (P = .10). Median overall survival (OS) was 2.2 years, with a 3 and 5-year OS of 43.4% and 31.6%, respectively. Disease-free survival (DFS) was 1.5 years, with 3 and 5-year DFS of 41.6% and 32%, respectively; no difference in OS and DFS between the 2 groups was found. ConclusionsConsidering the acceptable morbidity and mortality rate and the long-term survival, PN should not be excluded for selected patients with stage IIIA-N2 NSCLC as a matter of principle.

Outcomes in obese patients undergoing induction therapy for acute leukemia.

Obesity continues to be a growing epidemic in the United States. Guidelines published by American Society of Clinical Oncology in 2012 recommend dosing chemotherapy using actual body weight. However, the guidelines do not provide guidance for patients with hematologic malignancies. The objective of this study was to evaluate outcomes in obese patients undergoing induction chemotherapy for acute leukemia versus nonobese patients using actual body weight dosing. This single center retrospective chart review from November 2012 to August 2016 evaluated newly diagnosed leukemia patients who received induction chemotherapy dosed on actual body weight. The primary outcome was rate of complete remission following induction chemotherapy between obese patients versus nonobese patients. Secondary outcomes included time to absolute neutrophil count and platelet recovery, incidence of febrile neutropenia, clinical or microbiological infections, early (0-15 days) and in-hospital mortality, and overall survival at six months. Obese patients had similar rates of complete remission versus nonobese patients with acute myeloid leukemia (60% vs. 61.9%; p = 0.86) and acute lymphoblastic leukemia (87.5% vs. 92.8%; p = 0.31). Obese patients with acute myeloid leukemia were more likely to receive re-induction chemotherapy following 14-day bone marrow biopsy vs. nonobese patients (53.3% vs. 23.2%; p = 0.019). There were no significant differences in secondary outcomes in either group when comparing obese versus nonobese patients. Obese patients have similar rates of complete remission compared to nonobese patients following induction chemotherapy in acute leukemia. Continued research is needed to determine optimal dosing and long-term outcomes in this patient population.

Adverse Prognostic Factors of Advanced Esophageal Cancer in Patients Undergoing Induction Therapy with Docetaxel, Cisplatin and 5-Fluorouracil

The purpose of this study was to identify adverse prognostic factors for patients with advanced esophageal cancer undergoing chemotherapy with docetaxel, cisplatin and 5-fluorouracil (DCF). The study cohort comprised of 45 patients with advanced esophageal cancer who underwent induction DCF therapy followed by esophagectomy or chemoradiotherapy. Treatment outcomes and factors affecting early recurrence and death were analyzed. Overall 3-year survival was 61.4%, and 3-year disease-free survival was 44.7%. Clinically evident lymph node metastasis and clinical stage were associated with recurrence within 1 year and death within 2 years. Low maximum standardized uptake value (SUVmax) after induction DCF therapy and small decreases in SUVmax from pre- to post-DCF therapy were also predictors of recurrence and poor prognosis. Induction DCF therapy may be ineffective for advanced-stage esophageal cancer and clinical lymph node metastasis (≥N2, ≥stage IIIB). Moreover, small decreases in SUVmax DCF therapy are associated with early disease relapse and death.

Advances in the use of surgery and multimodality treatment for N2 non-small cell lung cancer

ABSTRACTIntroduction: Stage IIIA-N2 non-small cell lung cancer (NSCLC) represents a heterogeneous group of bronchogenic carcinomas with locoregional involvement. Different categories of N2 disease exist, ranging from unexpectedly encountered N2 involvement after detailed preoperative staging or ‘surprise’ N2, to potentially resectable disease treated within a combined modality setting, and finally, bulky N2 involvement treated by chemoradiation.Areas covered: Large randomised controlled trials and meta-analyses on stage IIIA-N2 NSCLC have been published but their implications for treatment remain a matter of debate. No definite recommendations can be provided as diagnostic and therapeutic algorithms vary according to local, national or international guidelines.Expert commentary: From the literature, it is clear that patients with stage IIIA-N2 NSCLC should be treated by combined modality therapy including chemotherapy, radiotherapy and surgery. The relative contribution of each modality has not been firmly established. For patients undergoing induction therapy, adequate restaging is important as only down-staged patients will clearly benefit from surgical resection. Each patient should be discussed within a multidisciplinary team to determine the best diagnostic and therapeutic approach according to the specific local expertise. In the near future, it might be expected that targeted therapies and immunotherapy will be incorporated as possible therapeutic options.

Extent of Lymphadenectomy Is Associated With Improved Overall Survival After Esophagectomy With or Without Induction Therapy

National Comprehensive Cancer Network (NCCN) guidelines recommend sampling 15 or more lymph nodes during esophagectomy. The proportion of patients meeting this guideline is unknown, as is its influence on overall survival (OS). Univariate analysis and logistic regression were performed to identify variables associated with sampling 15 or more lymph nodes among patients undergoing esophagectomy in the National Cancer Data Base (NCDB). The NCCN guideline was evaluated in Cox proportional hazards modeling, along with alternative lymph node thresholds. Positive to examined node (PEN) ratios were calculated, and OS was compared using Kaplan-Meier analysis. From 2006 to 2012, only 6,961 of 18,777 (37.1%) patients undergoing esophagectomy had sampling of 15 or more lymph nodes. Variables associated with sampling 15 or more lymph nodes included income greater than or equal to $38,000, procedure performed in an academic facility, and increasing clinical T and N stages. Induction therapy was associated with a decreased likelihood of 15 or more lymph nodes being sampled. The largest decrease in mortality hazard in patients undergoing upfront esophagectomy was detected when 25 lymph nodes or more were sampled (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.67-0.89; p < 0.001), whereas for patients undergoing induction therapy, sampling of 10 or 15 or more lymph nodes was associated with optimal survival benefit (HR, 0.81; 95% CI, 0.74-0.90; p < 0.001). PEN ratios of 0 to 0.10 were associated with maximum survival benefit among all patients undergoing esophagectomy. For patients with a PEN ratio of 0, increases in OS were detected with higher lymph node sampling (85.3 months for sampling of 20 or more lymph nodes versus 52.0 months for sampling 1-9 lymph nodes; p < 0.001). For patients undergoing upfront esophagectomy, there may be an increased survival benefit for examining 20 to 25 lymph nodes, which is higher than current recommendations. However, only a minority of patients are meeting current guidelines.

Interventions targeting absences increase adherence and reduce abandonment of childhood cancer treatment in El Salvador.

In El Salvador, about 200 new cases of pediatric cancer are diagnosed each year, and survival rates approach 70%. Although treatment is available at no cost, abandonment of therapy has remained at a steady yearly rate of 13% during the past decade. A time sensitive adherence tracking procedure (TS-ATP) was recently implemented to detect missed appointments, identify their causes, and intervene promptly. Procedure The study team was informed daily of patient/family failure to attend medical appointments in the pediatric oncology unit; the families were contacted and interviewed to ascertain and address the reasons. Patients who did not return after this initial contact were contacted again through local health clinics and municipalities. Law enforcement was a last resort for patients undergoing frontline treatment with a good prognosis., The system was adapted to clinical urgency: families of patients undergoing induction therapy were contacted within 24 hr, those in other therapy phases, within 48 hr, and those who had completed treatment, within one week. Reasons for absence were obtained by telephone or in person. The annual rate of abandonment was reduced from 13-3% during the 2 years period. There were 1,111 absences reported and 1,472 contacts with caregivers and institutions. The three main reasons for absences were financial needs (165, 23%), unforeseen barriers (116, 16%), and domestic needs (86, 12%). Use of the treatment adherence tracking system to locate and communicate with patients/families after missed appointments and the allocated aid stemming from these interviews substantially reduced abandonment and non-adherence.

A Phase II Feasibility Study of Prophylactic White Cell Transfusions for the Prevention of Infection in AML Patients Undergoing Induction Therapy

▪Patients with acute myeloid leukemia (AML) experience sustained and profound neutropenia during induction chemotherapy; infections remain the leading cause of morbidity and mortality in myelosuppressed leukemia patients. The current standard of care is to provide patients with broad-spectrum antibiotic, antifungal and antiviral therapy; however resistance to available anti-infective agents is increasing. Transfusion of functional non-irradiated allogeneic granulocytes to neutropenic leukemia patients may treat, delay or prevent infections in patients with leukemia, and importantly may also have anti-leukemia benefits.Patients treated at MD Anderson Cancer Center with a diagnosis of AML undergoing front-line AML therapy were eligible. Patients were required to be free of signs and symptoms of infection at the time of study entry, and have sufficient volunteer donors to administer prophylactic white cell transfusions approximately twice a week for six weeks. Allogeneic white cell transfusions (≥ 4 x 10¹⁰ cells per transfusion) were administered every 3-4 days during the induction chemotherapy cycle, so long as patients remained neutropenic with an absolute neutrophil count < 500. Prophylactic transfusions continued until the time of sustained ANC recovery, initiation of a new treatment regimen, or after the completion of 6 weeks on protocol.Herein we provide the results of the first 21 patients. Median age was 67 (range 23-78); 12 patients were male and 9 were female. All patients were enrolled at the time of initiation of AML induction therapy. Seven patients had a diagnosis of therapy-related AML (6 with an antecedent hematologic disorder and 1 with prior solid malignancy). Various treatment regimens were administered and are displayed in Table 1, along with cytogenetic and MD Anderson prognostic model classification.Patients received a median of 5 transfusions (range 0 – 11). Of 21 patients, 1 withdrew consent prior to the first transfusion, and 3 patients discontinued transfusions prior to the end of study (due to a diagnosis of pneumonia in one with potential concern for increased pulmonary toxicity with continued transfusions, and two at patient requests due to fevers and myalgias post transfusions).Median time to ANC recovery was 38 days (range 14 – 137) and platelet recovery 29 days (range 12 – 160), consistent with the elderly population and the allotted treatment regimens. All patients experienced at least one neutropenic fever, often within 48 hours of white cell administration. Documented infections included 2 instances of bacteremia (1 streptococcal and 1 E. coli), 2 urinary tract infections (both coagulase negative staphylococci), 8 cases of pneumonia (1 documented E. coli, 7 culture-negative and presumed fungal pneumonia per imaging). There was one patient with neutropenic colitis per imaging. There were no induction-related deaths. 8-week mortality was 5% (n=1) and 12-week mortality was 20% (n=4). With a median follow-up time on study of 20.3 weeks, overall survival is 67% with a median survival which has not yet been reached (Figure 1). Overall response to initial induction chemotherapy was 67% (9 CR, 1 CRi, 4 PR). A total of 15 patients (71%) ultimately attained a CR (after the first cycle or with additional cycles of therapy), and 4 patients received a stem cell transplant at the time of CR/CRi.In conclusion, prophylactic transfusion of allogeneic non-irradiated white blood cells for newly diagnosed AML patients during induction chemotherapy was associated with a decreased incidence of life-threatening infections, decreased induction mortality (6-week OS of 100%), and may also lead to improved remission rates and overall survival. This feasibility study has been expanded to enroll a total of 50 patients, with updated results to be provided at the annual meeting. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Long-Term Survival of Patients With pN2 Lung Cancer According to the Pattern of Lymphatic Spread

N2 involvement has dramatic consequences on the prognosis and management of patients with non-small cell lung cancer (NSCLC). N2-NSCLC may present with or without N1 involvement, constituting non-skip (pN1N2) and skip (pN0N2) diseases, respectively. As the prognostic impact of this subclassification is still a matter of debate, we analyzed the prognosis of pN2 patients according to the pN1-involvement and the number of N2-stations concerned. The medical records of consecutive patients who underwent surgery for pN2-NSCLC in 2 French centers between 1980 and 2009 were prospectively collected and retrospectively reviewed. Patients undergoing induction therapy, exploratory thoracotomy, incomplete mediastinal lymphadenectomy, or incomplete resections were excluded. The prognoses of pN1N2 and pN0N2 patients were first compared, and then deciphered according to the number of N2 stations involved (single-station: 1S, multi-station: 2S). All together, 871 patients underwent first-line complete surgical resection for pN2-NSCLC during the study period, including 258 pN0N2 (29.6%) and 613 pN1N2 (70.4%) patients. Mean follow-up was 72.8±48 months. Median, 5- and 10-year survivals were, respectively, 30 months, 34%, and 24% for pN0N2 and 20 months, 21%, and 14% for pN1N2 patients (p<0.001). Multivariate analysis revealed 3 different prognostic groups; ie, favorable in pN0N2-1S disease, intermediate in pN0N2-2S and pN1N2-1S diseases, and poor in pN1N2-2S disease (p<0.001). Among pN2 patients, the combination of N1 involvement (pN0N2 vs pN1N2) and number of involved N2 stations (1S vs 2S) are independent prognostic factors. These results might be taken into consideration to sub-classify the heterogeneous pN2-NSCLC group of patients.