Palliative chemotherapy during the last month of life.

e20662 Background: There is no uniform definition of medical futility, but most accept treatments offering no reasonable chance of benefiting patients will fall into this category. According to literature, chemotherapy given in the last month of life has little or no benefit to patients. Various studies suggest 9-43% of patients receive palliative chemotherapy during the last month of life. Methods: Retrospective analysis was done on electronic medical records of patients who received systemic anti cancer therapy (SACT) - cytotoxic and/or targeted therapy for solid or haematological malignancies at The Gold Coast hospital within one year period. Patients that died within 30 days of SACT administration were further classified based on their diagnosis, treatment intent, type of treatment and cause of death. Results: 770 patients received SACT between 1 November 2011 and 31 October 2012. 53 deaths (6.9%) occurred within 30 days of receiving SACT. 35 (66%) of those were due to progression of disease and 6 (11.3%) were treatment related. All treatment related deaths were due to neutropenic sepsis. For 12 deaths (22.7%), there was insufficient documentation to establish the cause of death. Only one patient with acute myeloid leukaemia (1.9%) died as a result of treatment given with curative intent. 20 patients (37.7%) were on combination treatment while 33 (62.3%) were treated with single agents. 42 patients (79.2%) received treatment that included intravenous agents, while remaining 11 patients (20.8%) were on oral treatment only. 37 patients (69.8%) were on cytotoxic treatment, 12 (22.6%) patients were on targeted therapy, and remaining 4 (7.6%) were on a combination protocol. Conclusions: Results of this audit show a lower number of patients who received palliative chemotherapy in a metropolitan public hospital in Australia during the last month of life. Defining the goal of treatment and assessing functional status of patients regularly while on treatment may help identify deteriorating patients and could avoid medically futile treatment. [Table: see text]

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Long-term cancer survivors treated with multiple courses of repeat radiation therapy

Radiation Oncology ◽

10.1186/s13014-021-01934-y ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Sebastian M. Christ ◽

Maiwand Ahmadsei ◽

Lotte Wilke ◽

Anja Kühnis ◽

Matea Pavic ◽

...

Keyword(s):

Overall Survival ◽

Median Overall Survival ◽

Anatomical Site ◽

Curative Intent ◽

Palliative Intent ◽

Number Of Patients ◽

Treatment Intent ◽

Long Term Survivors ◽

Median Interval

Abstract Introduction and background Through recent advances in cancer care, the number of long-term survivors has continuously increased. As a result, repetitive use of local radiotherapy for curative or palliative indications might have increased as well. This analysis aims to describe patterns of care and outcome of patients treated with multiple courses of repeat radiotherapy. Materials and methods All patients treated with radiotherapy between 2011 and 2019 at our department of Radiation Oncology were included into this analysis. A course of radiotherapy was defined as all treatment sessions to one anatomical site under one medical indication. Demographics, cancer and treatment characteristics and overall survival of patients having undergone multiple radiotherapy courses (minimum n = 5) were evaluated. Results The proportion of cancer patients treated with a minimum five courses of radiotherapy increased continuously from 0.9% in 2011 to 6.5% in 2019. In the 112 patients treated with a minimum of five radiotherapy courses, the primary tumor was lung in 41.9% (n = 47), malignant melanoma in 8.9% (n = 10) and breast in 8.0% (n = 9) of cases. A median interval of 3 years (maximum 8 years) elapsed between the first and the last radiotherapy course. The maximum number of courses in a single patient were n = 10. Treatment intent was curative or palliative in 46.4% and 53.6% for the first radiotherapy, respectively. The proportion of curative intent decreased to 11.6% at the 5th, and the last radiotherapy course was following a palliative intent in all patients. Five-year overall survival measured from the 1st radiotherapy course was 32.7%. Median overall survival was 3.3, 2.4, 1.3, and 0.6 years when measured from the 1st, the 1st palliative, the 5th and last course of radiotherapy, respectively. Discussion and conclusion A continuously increasing number of patients is treated with multiple courses of radiotherapy throughout their long-term cancer survivorship.

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Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma

Pharmaceuticals ◽

10.3390/ph14010051 ◽

2021 ◽

Vol 14 (1) ◽

pp. 51

Author(s):

Brinda Balasubramanian ◽

Simran Venkatraman ◽

Kyaw Zwar Myint ◽

Tavan Janvilisri ◽

Kanokpan Wongprasert ◽

...

Keyword(s):

Clinical Trials ◽

Targeted Therapy ◽

Drug Development ◽

Surgical Resection ◽

Treatment Options ◽

Standard Of Care ◽

Time Data ◽

Current Standard ◽

Innovative Drug ◽

Curative Intent

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.

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Management of Patients with Pancreatic Ductal Adenocarcinoma in the Real-Life Setting: Lessons from the French National Hospital Database

Cancers ◽

10.3390/cancers13143515 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3515

Author(s):

Christelle de la Fouchardière ◽

Mustapha Adham ◽

Anne-Marie Marion-Audibert ◽

Antoine Duclos ◽

Claude Darcha ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Real Life ◽

Ductal Adenocarcinoma ◽

University Hospitals ◽

National Hospital ◽

Curative Intent ◽

The Real ◽

Oncological Treatment ◽

Real Life Setting ◽

Number Of Patients

Pancreatic ductal adenocarcinoma (PDAC) remains a major public health challenge, and faces disparities and delays in the diagnosis and access to care. Our purposes were to describe the medical path of PDAC patients in the real-life setting and evaluate the overall survival at 1 year. We used the national hospital discharge summaries database system to analyze the management of patients with newly diagnosed PDAC over the year 2016 in Auvergne-Rhône-Alpes region (AuRA) (France). A total of 1872 patients met inclusion criteria corresponding to an incidence of 22.6 per 100,000 person-year. Within the follow-up period, 353 (18.9%) were operated with a curative intent, 743 (39.7%) underwent chemo- and/or radiotherapy, and 776 (41.4%) did not receive any of these treatments. Less than half of patients were operated in a high-volume center, defined by more than 20 PDAC resections performed annually, mainly university hospitals. The 1-year survival rate was 47% in the overall population. This study highlights that a significant number of patients with PDAC are still operated in low-volume centers or do not receive any specific oncological treatment. A detailed analysis of the medical pathways is necessary in order to identify the medical and territorial determinants and their impact on the patient’s outcome.

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Adverse reactions of targeted therapy in cancer patients: a retrospective study of hospital medical data in China

BMC Cancer ◽

10.1186/s12885-021-07946-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ruofei Du ◽

Xin Wang ◽

Lixia Ma ◽

Leon M. Larcher ◽

Han Tang ◽

...

Keyword(s):

Targeted Therapy ◽

Cancer Patients ◽

Adverse Reactions ◽

Cox Regression ◽

Target Therapy ◽

Skin Damage ◽

Data Set ◽

Patients With Cancer ◽

Number Of Patients ◽

Significant Difference

Abstract Background The adverse reactions (ADRs) of targeted therapy were closely associated with treatment response, clinical outcome, quality of life (QoL) of patients with cancer. However, few studies presented the correlation between ADRs of targeted therapy and treatment effects among cancer patients. This study was to explore the characteristics of ADRs with targeted therapy and the prognosis of cancer patients based on the clinical data. Methods A retrospective secondary data analysis was conducted within an ADR data set including 2703 patients with targeted therapy from three Henan medical centers of China between January 2018 and December 2019. The significance was evaluated with chi-square test between groups with or without ADRs. Univariate and multivariate logistic regression with backward stepwise method were applied to assess the difference of pathological characteristics in patients with cancer. Using the univariate Cox regression method, the actuarial probability of overall survival was performed to compare the clinical outcomes between these two groups. Results A total of 485 patients were enrolled in this study. Of all patients, 61.0% (n = 296) occurred ADRs including skin damage, fatigue, mucosal damage, hypertension and gastrointestinal discomfort as the top 5 complications during the target therapy. And 62.1% of ADRs were mild to moderate, more than half of the ADRs occurred within one month, 68.6% ADRs lasted more than one month. Older patients (P = 0.022) and patients with lower education level (P = 0.036), more than 2 comorbidities (P = 0.021), longer medication time (P = 0.022), drug combination (P = 0.033) and intravenous administration (P = 0.019) were more likely to have ADRs. Those with ADRs were more likely to stop taking (P = 0.000), change (P = 0.000), adjust (P = 0.000), or not take the medicine on time (P = 0.000). The number of patients with recurrence (P = 0.000) and metastasis (P = 0.006) were statistically significant difference between ADRs and non-ADRs group. And the patients were significantly poor prognosis in ADRs groups compared with non-ADRs group. Conclusion The high incidence of ADRs would affect the treatment and prognosis of patients with cancer. We should pay more attention to these ADRs and develop effective management strategies.

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Oral cobalamin supplementation in cats with hypocobalaminaemia: a retrospective study

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x16689406 ◽

2017 ◽

Vol 19 (12) ◽

pp. 1302-1306 ◽

Cited By ~ 7

Author(s):

Linda Toresson ◽

Joerg M Steiner ◽

Gunilla Olmedal ◽

MajBritt Larsen ◽

Jan S Suchodolski ◽

...

Keyword(s):

Retrospective Study ◽

Gastrointestinal Disease ◽

Oral Treatment ◽

Clinical Signs ◽

Reference Interval ◽

Inclusion Criteria ◽

Promising Alternative ◽

Once Daily ◽

Oral Supplementation ◽

Number Of Patients

Objectives The objective of the study was to evaluate whether oral cobalamin supplementation can restore normocobal-aminaemia in cats with hypocobalaminaemia and clinical signs of gastrointestinal disease. Methods This was a retrospective study based on a computerised database search for client-owned cats treated at Evidensia Specialist Animal Hospital, Helsingborg, Sweden, during the period December 2013 to August 2016. Inclusion criteria were cats with clinical signs of chronic enteropathy, an initial serum cobalamin concentration ⩽250 pmol/l (reference interval 214–738 pmol/l) and oral treatment with cobalamin tablets. Results Twenty-five cats met the inclusion criteria. The cats were treated with 0.25 mg cyanocobalamin tablets once daily. Serum cobalamin concentration was rechecked 27–94 days after continuous oral cobalamin supplementation. All cats had serum cobalamin concentrations above the reference interval after oral cobalamin supplementation. Median (range) serum cobalamin concentration was 128 pmol/l (111–250 pmol/l) prior to treatment and 2701 pmol/l (738–16,359 pmol/l) after supplementation. This difference was statistically significant ( P <0.0001). Conclusions and relevance Our results suggest that oral cobalamin supplementation is effective in increasing serum cobalamin to supranormal concentrations in cats with hypocobalaminaemia. Thus, oral cobalamin supplementation is a promising alternative to parenteral administration. Prospective comparative studies in cats being treated with parenteral vs oral cobalamin supplementation in a larger number of patients are warranted before oral supplementation can be recommended for routine use.

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Off-label targeted therapy (TT) use in recurrent/metastatic NSCLC.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18688 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18688-e18688

Author(s):

Victoria Wang ◽

Chenming Cui ◽

Lei Yang ◽

Gerald Li ◽

Alexa Betzig Schrock ◽

...

Keyword(s):

Targeted Therapy ◽

Clinical Efficacy ◽

Real World ◽

Survival Advantage ◽

Genomic Alteration ◽

Genomic Profiling ◽

Off Label ◽

Number Of Patients ◽

Tier System ◽

Line Of Therapy

e18688 Background: Comprehensive genomic profiling (CGP) is an established diagnostic approach to select patients for TT. As CGP gains wide adoption, an increasing number of patients are found to harbor driver mutations for which no approved TT is available. This is often addressed through use of matched TKI and mAb approved for other mutations or anatomic sites. In this work, we examined the clinical efficacy of off-label TT in R/M NSCLC. Methods: Using a de-identified NSCLC clinico-genomic database (CGDB), we identified 6590 NSCLC patients who underwent Foundation Medicine CGP, of whom 17.8% harbored an actionable genomic alteration (GA) for which an FDA-approved TT was available and 2% (133) whose GA (MET ex-14, uncommon EGFRm, EGFR ex20ins, HER2 amp/mut, RET fusion, BRAF class 2/3) lacked an FDA-approved TT (62 in 1L and 71 in ≥2L ) who received matched off-label TT. ESMO Scale for Clinical Actionability (ESCAT) was used to grade levels of evidence. For patients who progressed on initial chemotherapy (range 2 – 9 lines, median 3), we calculated clinical efficacy using the ratio of real world PFS on targeted therapy (rw-PFS2) to rw-PFS on the last prior line of therapy (rw-PFS1) and used a cut-off of PFS2/PFS1 > 1.3 to determine off-label drug efficacy. Results: Of the 133 patients reviewed, 72 were classified as ESCAT level IB (uncommon EGFRm, MET-ex14), 45 IIB (HER2m/amp, EGFR ex-20ins), 7 IC (RET fusions). PFS varied significantly by mutation and line of therapy (table 1) with uncommon EGFRm+ and MET-ex14 exhibiting best response while EGFR ex20 ins, BRAF class 2/3 and HER2 amp fared significantly worse. 55.8% of the patients (39 of 71) reached a PFS2/PFS1 ratio > 1.3 (two-sided 95% CI, 45.3 % – 68.7 %), ranging from 93% in uncommon EGFRm+ down to 20% in HER2 amp and 44% in ex20ins. Conclusions: We provide real-world evidence to assess off-label TT in NSCLC. Clinical benefit derived from off-label TT is unevenly distributed across various mutations with most survival advantage accruing to specific mutations (MET-ex14 and uncommon EGFRm) at the expense of others (HER2 amp). Survival advantage was highly influenced by two factors: A) the timing of CGP with the earlier recipients of genomic profiling achieving better outcome, B) the identity of the driver mutation, highlighting the role of clinical actionability tier system to define level of evidence supporting such intervention.[Table: see text]

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First-Line Palliative Chemotherapy for Esophageal and Gastric Cancer: Practice Patterns and Outcomes in the General Population

JCO Oncology Practice ◽

10.1200/op.20.00397 ◽

2021 ◽

pp. OP.20.00397

Author(s):

Shaila J. Merchant ◽

Weidong Kong ◽

Bishal Gyawali ◽

Timothy P. Hanna ◽

Wiley Chung ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Trials ◽

General Population ◽

Palliative Chemotherapy ◽

Administrative Databases ◽

Routine Practice ◽

First Line ◽

Medical Oncologist ◽

Cancer Specific Survival ◽

Curative Intent

PURPOSE: Clinical trials have shown that palliative chemotherapy (PC) improves survival in patients with incurable esophageal and gastric cancer; however, outcomes achieved in routine practice are unknown. We describe treatment patterns and outcomes among patients treated in the general population of Ontario, Canada. METHODS: The Ontario Cancer Registry was used to identify patients with esophageal or gastric cancer from 2007 to 2016, and data were linked to other health administrative databases. Patients who received curative-intent surgery or radiotherapy were excluded. Factors associated with the receipt of PC were determined using logistic regression. First-line PC regimens were categorized, and trends over time were reported. Survival was determined using the Kaplan-Meier method. RESULTS: The cohort included 9,848 patients; 22% (2,207 of 9,848) received PC. Patients receiving PC were younger (mean age, 63 v 74 years; P < .0001) and more likely male (71% v 65%; P < .0001). Thirty-seven percent of non-PC patients saw a medical oncologist in consultation. Over the study period, utilization of PC increased (from 11% in 2007 to 19% in 2016; P < .0001), whereas the proportion of patients receiving triplet regimens decreased (65% in 2007 to 56% in 2016; P = .04). In the PC group, the median overall and cancer-specific survival from treatment initiation was 7.2 months. CONCLUSION: One fifth of patients with incurable esophageal and gastric cancer in the general population receive PC. Median survival of patients treated in routine practice is inferior to that in clinical trials. Only one third of patients not treated with PC had consultation with a medical oncologist. Further work is necessary to understand low utilization of PC and medical oncology consultation in this patient population.

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What's new in the pathogenesis and treatment of therapy-related myeloid neoplasms

Blood ◽

10.1182/blood.2021010764 ◽

2021 ◽

Author(s):

Maria Teresa Voso ◽

Giulia Falconi ◽

Emiliano Fabiani

Keyword(s):

Atomic Bomb ◽

Therapeutic Option ◽

Familial Cancer ◽

Autoimmune Disorder ◽

New Drugs ◽

Cancer Genes ◽

Curative Intent ◽

Tp53 Mutations ◽

Myeloid Neoplasms ◽

Cytotoxic Treatment

Therapy-related myeloid neoplasms (t-MN) include diseases onsetting in patients treated with chemo- and/or radiotherapy for a primary cancer, or an autoimmune disorder. Genomic variants, in particular in familial cancer genes, may play a predisposing role. Recent advances in deep sequencing techniques have shed light on the pathogenesis of t-MN, identifying clonal hematopoiesis of indeterminate potential (CHIP) as a frequent first step in the multi-hit model of t-MN. CHIP is often detectable prior to any cytotoxic treatment, probably setting the fertile genomic background for secondary leukemogenesis. The evolution pattern towards t-MN is then a complex process, shaped by the type of cancer therapy, the aging process, and the individual exposures, that favor additional hits, such as the acquisition of TP53 mutations and unfavorable karyotype abnormalities. The pathogenesis of t-MN differs from MN associated with environmental exposure. Indeed, the genetic aberration patterns of MN developing in atomic bomb survivors show few mutations in classical DNA methylation genes, and a high prevalence of 11q and ATM alterations, together with TP53 mutations. Survival in t-MN is poor. In addition to the biology of t-MN, the patient's previous disease history and the remission status at t-MN diagnosis are significant factors contributing to unfavorable outcome. New drugs active in secondary leukemias include CPX-351, or venetoclax in combination with hypomethylating agents, monoclonal antibodies as magrolimab, or targeted drugs against pathogenic mutations. Allogeneic stem cell transplantation remains the best currently available therapeutic option with curative intent for fit patients with unfavorable genetic profiles.

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Signet ring cell carcinoma of the rectum: atypical metastatic presentation

BMJ Case Reports ◽

10.1136/bcr-2018-229135 ◽

2019 ◽

Vol 12 (4) ◽

pp. e229135 ◽

Cited By ~ 1

Author(s):

Mariana Morales-Cruz ◽

Noel Salgado-Nesme ◽

Alicia Maybi Trolle-Silva ◽

Jorge Humberto Rodríguez-Quintero

Keyword(s):

Cell Carcinoma ◽

Rectal Neoplasms ◽

Palliative Chemotherapy ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Curative Intent ◽

Carcinoma Of The Rectum ◽

Common Cancer ◽

Signet Ring ◽

Ring Cell

Colorectal cancer is the third most common cancer in the world and the fourth most common cause of death related to cancer. Signet ring cell carcinoma represents an uncommon histological type for rectal cancer with less than 1% of all rectal neoplasms. It usually behaves aggressively and has an inferior prognosis. We present the case of a young man diagnosed with signet ring cell rectal carcinoma. He underwent neoadjuvant therapy with partial response, had surgery with curative intent and showed local recurrence after only 3 months. Disease progression happened only weeks after recurrence with metastasis to vertebrae, extraocular muscles, bone marrow and skin. He is currently receiving palliative chemotherapy.

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Changing Patterns of Mortality in Gaucher Disease Prior to and Following the Advent of Enzyme Replacement Therapy.

Blood ◽

10.1182/blood.v104.11.3799.3799 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3799-3799

Author(s):

Neal J. Weinreb ◽

Robert E. Lee

Keyword(s):

Cardiovascular Disease ◽

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Cause Of Death ◽

Gaucher Disease ◽

Age At Death ◽

Enzyme Replacement ◽

Number Of Patients ◽

Changing Patterns ◽

The Impact

Abstract Enzyme replacement therapy (ERT) with exogenous glucosylceramide β-glucosidase (alglucerase, [Ceredase®] or imiglucerase, [Cerezyme®]) has been shown to improve anemia, thrombocytopenia, hepatosplenomegaly, bone symptoms and quality of life in patients with Gaucher disease. However, the impact of ERT on mortality has not been assessed since the inception of ERT in 1991. Data from the epoch prior to the availability of ERT were obtained from the University of Pittsburgh Gaucher Disease Registry. Data from the time period following the advent of ERT were obtained from the International Collaborative Gaucher Group (ICGG) Gaucher Registry and the Ceredase/Cerezyme pharmacovigilance database (Genzyme Corporation). Age of death was obtained for patients with reported Type 1 (non-neuronopathic) Gaucher disease. Only patients with a known cause of death were included in this analysis. Pre-ERT Era (R.E.L.) Post-ERT Era Number of patients 31 137 Treated with ERT No Yes Mean age at death (years) 53.2 55.6 Range of age at death (years) 3–85 0.2–89 Cause of death due to: n % n % • Gaucher disease 4 12.9% 1 0.7% • Leukemia 3 9.7% 7 5.1% • Lymphoma 1 3.2% 3 2.2% • Myeloma 3 9.7% 1 0.7% • Solid tumor 12 38.7% 17 12.4% • Hemorrhage 1 3.2% 14 10.2% • Thromboembolism 0 0.0% 4 2.9% • Other cardiovascular disease 2 6.5% 26 19.0% • Infectious disease 3 9.7% 6 10.9% • Other causes 2 6.5% 49 35.8% These descriptive data collected prior to the advent of ERT and following approval of ERT in 1991 raise intriguing questions about the changing pattern of mortality in Gaucher disease. Any direct comparison of these populations must be qualified by the possibility of detection bias or a cohort effect. Therefore, pending further information, it is difficult to attribute significance to the difference in mean age at death between the two populations. However, there have been shifts in the pattern of the causes of death. Most notably, deaths due to the primary manifestations of Gaucher disease and to hematologic cancers and solid tumors appear substantially less common in the post-ERT era whereas the proportion of deaths due to cardiovascular disease and other causes appears to be increasing. More accurate estimates of the patterns of mortality in Gaucher disease remain to be determined, particularly for the pre-ERT era. Additional studies of the changing patterns of mortality in Gaucher disease are ongoing.

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