ResearchPad - chemotherapy https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Survival of glioblastoma treated with a moderately escalated radiation dose—Results of a retrospective analysis]]> https://www.researchpad.co/article/elastic_article_14700 Glioblastoma (GBM) has the highest fatality rate among primary malignant brain tumors and typically tends to recur locally just adjacent to the original tumor site following surgical resection and adjuvant radiotherapy. We conducted a study to evaluate the survival outcomes between a standard dose (≤ 60 Gy) and moderate radiation dose escalation (>60 Gy), and to identify prognostic factors for GBM. We retrospectively reviewed the medical records of primary GBM patients diagnosed between 2005 and 2016 in two referral hospitals in Taiwan. They were identified from the cancer registry database and followed up from the date of diagnosis to October 2018. The progression-free survival (PFS) and overall survival (OS) were compared between the two dose groups, and independent factors for survival were analyzed through Cox proportional hazard model. We also affirmed the results using Cox regression with least absolute shrinkage and selection operator (LASSO) approach. From our cancer registry database, 142 GBM patients were identified, and 84 of them fit the inclusion criteria. Of the 84 patients, 52 (62%) were males. The radiation dose ranged from 50.0 Gy to 66.6 Gy, but their treatment volumes were similar to the others. Fifteen (18%) patients received an escalated dose boost >60.0 Gy. The escalated group had a longer median PFS (15.4 vs. 7.9 months, p = 0.01 for log-rank test), and a longer median OS was also longer in the escalation group (33.8 vs. 12.5 months, p <0.001) than the reference group. Following a multivariate analysis, the escalated dose was identified as a significant predictor for good prognosis (PFS: hazard ratio [HR] = 0.48, 95% confidence interval [95%CI]: 0.23–0.98; OS: HR = 0.40, 95%CI: 0.21–0.78). Using the LASSO approach, we found age > 70 (HR = 1.55), diagnosis after 2010 (HR = 1.42), and a larger radiation volume (≥ 250ml; HR = 0.81) were predictors of PFS. The escalated dose (HR = 0.47) and a larger radiation volume (HR = 0.76) were identified as predictors for better OS. Following detailed statistical analysis, a moderate radiation dose escalation (> 60 Gy) was found as an independent factor affecting OS in GBM patients. In conclusion, a moderate radiation dose escalation (> 60 Gy) was an independent predictor for longer OS in GBM patients. However, prospective studies including more patients with more information, such as molecular markers and completeness of resection, are needed to confirm our findings.

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<![CDATA[Recent Progress in Anti-Influenza Chemotherapy]]> https://www.researchpad.co/article/N291f3eed-ea2a-4fa6-a595-d92832f24bd9

Influenza virus infections in high risk individuals, such as infants, the elderly, and patients with cardiopulmonary disorders or immunocompromised states, cause severe manifestations which often result in fatalities. The emergence of a new antigen type of influenza A virus (H5N1) in Hong Kong during 1997 and 1998 threatened a possible pandemic of a new influenza infection.

The investigation for anti-influenza chemotherapies has progressed in the last decade whereas clinical trials of new compounds have been limited to amantadine, rimantadine and ribavirin. Fusion inhibitors which directly inhibit conformational change of haemagglutinin (HA), protease inhibitors which inhibit cleavage of HA to HA1 and HA2, RNA transcription inhibitors which inhibit cap formation of mRNA and antisense oligonucleotides targeted at mRNA of PB2 (a part of viral RNA polymerase) have been reported, in their development phases.

Recently, 2 neuraminidase (NA) inhibitors, zanamivir and oseltamivir (GS 4104), were used in clinical trials for the treatment of patients with influenza. Both agents showed promising results. A polyoxometalate, PM-523, inhibits fusion between the virus envelope and cell membrane and inhibits the penetration of the virus into cells. This compound has shown potent anti-influenza activity and synergistic inhibitory activity in combination with ribavirin or zanamivir in vitro and in vivo.

Resistant strains for zanamivir, oseltamivir or PM-523 have been isolated. The analysis of mutation points of these strains have contributed to the investigation of the antiviral mechanisms of action of these compounds and the mechanism of resistance of the mutants to these compounds.

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<![CDATA[Efficacy of adjuvant chemotherapy with S-1 in stage II oral squamous cell carcinoma patients: A comparative study using the propensity score matching method]]> https://www.researchpad.co/article/N83ad1f15-cdbb-4f4c-8d9c-388a45a97cce

It has been reported that 20% of early-stage oral squamous cell carcinoma (OSCC) patients treated with surgery alone (SA) may exhibit postoperative relapse within 2–3 years and have poor prognoses. We aimed to determine the safety of S-1 adjuvant chemotherapy and the potential differences in the disease-free survival (DFS) between patients with T2N0 (stage II) OSCC treated with S-1 adjuvant therapy (S-1) and those treated with SA. This single-center retrospective cohort study was conducted at Kumamoto University, between April 2004 and March 2012, and included 95 patients with stage II OSCC. The overall cohort (OC), and propensity score-matched cohort (PSMC) were analyzed. In the OC, 71 and 24 patients received SA and S-1, respectively. The time to relapse (TTR), DFS, and overall survival were better in the S-1 group, but the difference was not significant. In the PSMC, 20 patients each received SA and S-1. The TTR was significantly lower in the S-1 group than in the SA group, while the DFS was significantly improved in the former. S-1 adjuvant chemotherapy may be more effective than SA in early-stage OSCC.

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<![CDATA[Long-term visual acuity in patients with optic pathway glioma treated during childhood with up-front BB-SFOP chemotherapy—Analysis of a French pediatric historical cohort]]> https://www.researchpad.co/article/5c8c1959d5eed0c484b4d486

Background

Visual outcome is one of the main issues in the treatment of optic pathway glioma in childhood. Although the prognostic factors of low vision have been discussed extensively, no reliable indicators for visual loss exist. Therefore, we aimed to define initial and evolving factors associated with long-term vision loss.

Methods

We conducted a multicenter historical cohort study of children treated in France with up-front BB-SFOP chemotherapy between 1990 and 2004. Visual acuity performed at the long-term follow-up visit or within 6 months prior was analyzed. Logistic regression analysis was used to estimate the effects of clinical and radiological factors on long-term visual outcome.

Findings

Of the 180 patients in the cohort, long-term visual acuity data were available for 132 (73.3%) patients (median follow-up: 14.2 years; range: 6.1–25.6). At the last follow-up, 61/132 patients (46.2%) had impaired vision, and 35 of these patients (57.3%) were partially sighted or blind. Multivariate analysis showed that factors associated with a worse prognosis for long-term visual acuity were an age at diagnosis of < 1 year (OR 3.5 [95% CI: 1.1–11.2], p = 0.04), tumor extent (OR 4.7 [95% CI: 1.2–19.9], p = 0.03), intracranial hypertension requiring one or more surgical procedures (OR 5.6 [95% CI: 1.8–18.4], p = 0.003), and the need for additional treatment after initial BB-SFOP chemotherapy (OR 3.5 [95% CI: 1.1–11.9], p = 0.04). NF1 status did not appear as a prognostic factor, but in non-NF1 patients, a decrease in tumor volume with contrast enhancement after BB-SFOP chemotherapy was directly associated with a better visual prognosis (OR 0.8 [95% CI: 0.8–0.9], p = 0.04).

Interpretation

Our study confirms that a large proportion of children with optic pathway glioma have poor long-term outcomes of visual acuity. These data suggest new prognostic factors for visual acuity, but these results need to be confirmed further by large- and international-scale studies.

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<![CDATA[Tailored NEOadjuvant epirubicin, cyclophosphamide and Nanoparticle Albumin-Bound paclitaxel for breast cancer: The phase II NEONAB trial—Clinical outcomes and molecular determinants of response]]> https://www.researchpad.co/article/5c6f152dd5eed0c48467ae8b

Background

This study evaluated the feasibility of achieving high response rates in stage II or III breast cancer by tailoring neoadjuvant therapy using clinical and histopathological features and the Oncotype DX Breast Recurrence Score. Genomic determinants of response and resistance were also explored.

Patients and outcome measures

Fifty-one patients were enrolled. The primary cohort comprised 40 patients: 15 human epidermal growth factor receptor type 2 (HER2)-amplified; 15 triple-negative (TNBC); and ten hormone receptor (HR)-positive, HER2-non-amplified tumours; with recurrence scores ≥25. Patients were treated with epirubicin and cyclophosphamide, followed by nab-paclitaxel, with the addition of trastuzumab if HER2-amplified. The primary endpoint was pathological complete response (pCR) in the breast. Pre- and post-treatment tumour samples underwent variant burden, gene and gene pathway, mutational signature profile and clonal evolution analyses.

Results

The pCR rates were: overall 55% (n = 22), HER2-amplified 80% (n = 12), triple-negative 46% (n = 7) and HR-positive, HER2-non-amplified 30% (n = 3). Grade 3 or 4 adverse events included febrile neutropenia (8%), neutropenia (18%), sensory neuropathy (5%), deranged transaminases (5%), fatigue (2%), diarrhoea (2%), and pneumothorax (2%). Molecular analyses demonstrated strong similarities between residual disease and matched primary tumour. ATM signalling pathway alterations and the presence of a COSMIC Signature 3 implied the majority of tumours contained some form of homologous repair deficiency. ATM pathway alterations were identified in the subset of TNBC patients who did not achieve pCR; Signature 3 was present in both pCR and non-pCR subgroups. Clonal evolution analyses demonstrated both persistence and emergence of chemoresistant clones.

Conclusions

This treatment regime resulted in a high rate of pCR, demonstrating that tailored neoadjuvant therapy using a genomic recurrence score is feasible and warrants further investigation. Molecular analysis revealed few commonalities between patients. For TNBC future clinical gains will require precision medicine, potentially using DNA sequencing to identify specific targets for individuals with resistant disease.

Trial registration

Clinicaltrials.gov NCT01830244

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<![CDATA[Machine learning models for predicting post-cystectomy recurrence and survival in bladder cancer patients]]> https://www.researchpad.co/article/5c76fe04d5eed0c484e5b2b2

Currently in patients with bladder cancer, various clinical evaluations (imaging, operative findings at transurethral resection and radical cystectomy, pathology) are collectively used to determine disease status and prognosis, and recommend neoadjuvant, definitive and adjuvant treatments. We analyze the predictive power of these measurements in forecasting two key long-term outcomes following radical cystectomy, i.e., cancer recurrence and survival. Information theory and machine learning algorithms are employed to create predictive models using a large prospective, continuously collected, temporally resolved, primary bladder cancer dataset comprised of 3503 patients (1971-2016). Patient recurrence and survival one, three, and five years after cystectomy can be predicted with greater than 70% sensitivity and specificity. Such predictions may inform patient monitoring schedules and post-cystectomy treatments. The machine learning models provide a benchmark for predicting oncologic outcomes in patients undergoing radical cystectomy and highlight opportunities for improving care using optimal preoperative and operative data collection.

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<![CDATA[Preliminary results of identification and quantification of paclitaxel and its metabolites in human meconium from newborns with gestational chemotherapeutic exposure]]> https://www.researchpad.co/article/5c76fe5dd5eed0c484e5b96b

Objective

Cancer diagnosis during pregnancy occurs in 1 out of 1000 pregnancies with common malignancies including breast and hematological cancers. Fetal exposure to currently utilized agents is poorly described. We directly assessed fetal exposure by screening meconium from 23 newborns whose mothers had undergone treatment for cancer during pregnancy.

Study design

Meconium was collected from newborns whose mothers were diagnosed with cancer during pregnancy and underwent chemotherapy in the second or third trimester as part of the Cancer and Pregnancy Registry. We conducted screening of 23 meconium samples for chemotherapeutics and known metabolites of chemotherapeutics by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Putative identification of paclitaxel and/or its metabolites was made in 8 screened samples. In positively screened samples, we quantified paclitaxel, 3’-p-hydroxypaclitaxel, and 6α-hydroxypaclitaxel by stable isotope dilution-LC-HRMS.

Results

Mean (standard deviation) levels of paclitaxel in positively screened samples were 399.9 (248.6) pg/mg in meconium samples from newborn born to mothers that underwent chemotherapy during pregnancy. 3’-p-hydroxypaclitaxel and 6α-hydroxypaclitaxel mean levels were 105.2 (54.6) and 113.4 (48.9) pg/mg meconium, respectively.

Conclusion

Intact paclitaxel, 3’-p-hydroxypaclitaxel, and 6α-hydroxypaclitaxel were detected in meconium, providing unambiguous confirmation of human fetal exposure. Variability in meconium levels between individuals may indicate a potential for reducing fetal exposure based on timing, dosing, and individual characteristics. This preliminary study may provide an approach for examining the effects of cancer diagnosis during pregnancy on other outcomes by providing a measure of direct fetal exposure.

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<![CDATA[Prediction of local recurrence risk after neoadjuvant chemotherapy in patients with primary breast cancer: Clinical utility of the MD Anderson Prognostic Index]]> https://www.researchpad.co/article/5c5ca2e2d5eed0c48441ec55

Background

Locoregional recurrence after neoadjuvant chemotherapy for primary breast cancer is associated with poor prognosis. It is essential to identify patients at high risk of locoregional recurrence who may benefit from extended local therapy. Here, we examined the prediction accuracy and clinical applicability of the MD Anderson Prognostic Index (MDAPI).

Methods

Prospective clinical data from 456 patients treated between 2003 and 2011 was analyzed. The Kaplan-Meier method was used to examine the probabilities of locoregional recurrence, local recurrence and distant metastases according to individual prognosis score, stratified by type of surgery (breast conserving therapy or mastectomy). The possible confounding of the relationship between recurrence risk and MDAPI by established risk factors was accounted for in multiple survival regression models. To define the clinical utility of the MDAPI we analyzed its performance to predict locoregional recurrence censoring patients with prior or simultaneous distant metastases.

Results

Mastectomized patients (42% of the patients) presented with more advanced tumor stage, lower tumor grade, hormone-receptor positive disease and consequently lower pathological complete response rates. Only a few patients presented with high-risk scores (2,7% MDAPI≥3). All patients with high-risk MDAPI score (MDAPI ≥3) who developed locoregional recurrence were simultaneously affected by distant metastases.

Conclusion

Our data do not support a clinical utility of the MDAPI to guide local therapy.

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<![CDATA[Current management of cervical cancer in Poland—Analysis of the questionnaire trial for the years 2002-2014 in relation to ASCO 2016 recommendations]]> https://www.researchpad.co/article/5c5ca28fd5eed0c48441e638

Objectives

To assess the survival of patients with cervical cancer (CC). Since the recommendations concerning cervical cancer management adopted by Polish medical societies do not differ significantly from the ESGO or non-European guidelines, and the fact that evaluation of the system for CC treatment in Poland, as well as the mortality rate of Polish women with CC, which is 70% higher than the average for European Union (EU) countries, justifies the hypothesis that treatment of CC in Poland deviates from the Polish and international recommendations. This article puts forward the current management of cervical cancer in Poland and discusses it in the context of ASCO guidelines.

Material and methods

A survey retrospective multicenter analysis of the medical records of 1247 patients with cervical cancer who underwent treatment for disease and who had completed at least two years of follow-up.

Results

Although concurrent radiotherapy and chemotherapy is a standard treatment of FIGO IB to IVA cervical cancer patients in enhanced- and maximum-resources settings, in our analysis, we found that the percentage of women subjected to chemotherapy was lower than in countries where total survival rates were lower.

Conclusion

Within the IA to II A cervical cancer patients studied group, the methods of treatment remained in line with ASCO guidelines for countries with the highest standard of care.

Although concurrent radiotherapy and chemotherapy is a standard treatment of FIGO IB to IVA cervical cancer patients in enhanced- and maximum-resources settings, in our analysis, we found that the percentage of women subjected to chemotherapy was lower than in countries where total survival rates were lower.

Our findings, together with the inconsistencies within the cervical cancer screening program, may be one of the explanations of poorer survival rate of women with cervical cancer in Poland.

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<![CDATA[Impact of time to local recurrence on the occurrence of metastasis in breast cancer patients treated with neoadjuvant chemotherapy: A random forest survival approach]]> https://www.researchpad.co/article/5c5217b2d5eed0c4847943bc

Background

We studied the relationship between time to ipsilateral breast tumor recurrence (IBTR) and distant metastasis-free survival (DMFS) in patients with breast cancer treated by neoadjuvant chemotherapy (NAC).

Methods

Between 2002 and 2012, 1199 patients with primary breast cancer were treated with NAC. Clinical, radiological and pathological data were retrieved from medical records. Multivariate analysis was performed with the random survival forest (RSF) method, to evaluate the relationship between time to local recurrence and DMFS.

Results

Time to IBTR, local recurrence and molecular subtype were the factors most strongly associated with DMFS. In the total population, DMFS increased linearly with recurrence time, up to 50 months. For recurrences after 50 months, DMFS was similar for all times to recurrence. Considering molecular subtypes separately, the threshold was similar for the TNBC subtype (50 months), but appeared to occur later for the luminal and HER2-positive subtypes (75 months).

Conclusion

A threshold of 50 months seems to differentiate between early and late recurrences and could be used to guide the medical management of local breast tumour recurrences.

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<![CDATA[Colonization with multidrug resistant organisms determines the clinical course of patients with acute myeloid leukemia undergoing intensive induction chemotherapy]]> https://www.researchpad.co/article/5c52185cd5eed0c484797d9f

Introduction

The global spread of multidrug-resistant organisms (MDRO) complicates treatment and isolation measures in hospitals and has shown to increase mortality. Patients with disease- or therapy-related immunodeficiency are especially at risk for fatal infections caused by MDRO. The impact of MDRO colonization on the clinical course of AML patients undergoing intensive induction chemotherapy—a potentially curative but highly toxic treatment option—has not been systematically studied.

Materials & methods

312 AML patients undergoing intensive induction chemotherapy between 2007 and 2015 were examined for MDRO colonization. Patients with evidence for MDRO before or during the hospital stay of induction chemotherapy were defined as colonized, patients who never had a positive swab for MDRO were defined as noncolonized.

Results

Of 312 AML patients 90 were colonized and 130 were noncolonized. Colonized patients suffered from significantly more days with fever, spent more days on the intensive care unit and had a higher median C-reactive protein value during the hospital stay. These findings did not result in a prolonged length of hospital stay or an increased mortality rate for colonized patients. However, in a subgroup analysis, patients colonized with carbapenem-resistant enterobacteriaceae (CRE) had a significantly reduced 60- and 90-day, as well as 1- and 2-year survival rates when compared to noncolonized patients.

Conclusion

Our analysis highlights the importance of intensive MDRO screening especially in patients with febrile neutropenia since persisting fever can be a sign of MDRO-colonization. CRE-colonized patients require special surveillance, since they seem to be at risk for death.

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<![CDATA[Profile of treatment-related complications in women with clinical stage IB-IIB cervical cancer: A nationwide cohort study in Japan]]> https://www.researchpad.co/article/5c3d00fed5eed0c4840375f7

Objective

To examine clinico-pathological factors associated with surgical complications and postoperative therapy for clinical stage IB-IIB cervical cancer.

Methods

This nationwide multicenter retrospective study examined women with clinical stage IB-IIB cervical cancer who underwent radical hysterectomy plus pelvic and/or para-aortic lymphadenectomy between 2008–2009 at 87 institutions of the Japanese Gynecologic Oncology Group (n = 693). Multivariate models were used to identify independent predictors of perioperative grade 3–4 complications and bladder dysfunction.

Results

The overall intraoperative and postoperative complication rates were 3.3% and 9.8%, respectively. Clinical stage was not associated with perioperative complications (P = 0.15). Radiotherapy-based adjuvant therapy was significantly associated with an increased risk of postoperative complications (radiotherapy alone: adjusted-odds ratio [OR] 3.19, 95% confidence interval [CI] 1.46–6.99, P = 0.004; radiotherapy plus chemotherapy: adjusted-OR 3.26, 95%CI 1.66–6.41, P = 0.001), whereas chemotherapy was not (P = 0.45). Nerve-sparing surgery significantly reduced the risk of postoperative bladder dysfunction (adjusted-OR 0.57, 95%CI 0.37–0.90, P = 0.02) whereas adjuvant chemotherapy increased the risk of bladder dysfunction (adjusted-OR 2.06, 95%CI 1.16–3.67, P = 0.01). Among women receiving adjuvant chemotherapy, nerve-sparing radical hysterectomy significantly reduced the risk of bladder dysfunction (15.0% versus 32.9%, OR 0.31, 95%CI 0.14–0.68, P = 0.004). After propensity score matching, survival outcomes were similar with both types of adjuvant therapy (radiotherapy-based versus chemotherapy, P>0.05).

Conclusion

Our study highlighted two distinct complication profiles of adjuvant therapy after radical hysterectomy for clinical stage IB-IIB cervical cancer, with radiotherapy increasing grade 3–4 adverse events and chemotherapy increasing bladder dysfunction. In this setting, nerve-sparing surgery may be useful if chemotherapy is being considered for adjuvant therapy.

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<![CDATA[Real-world management of patients with epidermal growth factor receptor (EGFR) mutation-positive non–small-cell lung cancer in the USA]]> https://www.researchpad.co/article/5c390bfcd5eed0c48491f430

Background

Randomized phase III trials have established the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as first-line treatment for EGFR mutation-positive advanced non–small-cell lung cancer (EGFR Mut+ NSCLC). This retrospective cohort study examined the management patterns and outcomes of patients with EGFR Mut+ NSCLC in a real-world setting.

Materials and methods

Data were extracted from the US Flatiron Electronic Health Record-derived database. Adult patients with stage IIIB/IV EGFR Mut+ NSCLC (exon 19 deletion or exon 21 L858R mutation) who had received first-line systemic therapy between 2011 and 2016 were included. Demographic and clinical characteristics were analyzed. Outcomes evaluated were time to next treatment (a surrogate for progression-free survival) and overall survival.

Results

Of the 22,258 patients with advanced NSCLC in the database, 961 met the inclusion criteria. Median age was 69.0 years (range: 61–78) and the majority were female (68.0%), with stage IV (93.9%), non-squamous cell carcinoma (97.4%). EGFR tyrosine kinase inhibitors were the most widely prescribed first-line therapy (72.8%). The likelihood of receiving an EGFR tyrosine kinase inhibitor or chemotherapy was unaffected by the type of medical insurance patients had. Patients treated with an EGFR tyrosine kinase inhibitor had significantly longer time to next treatment than those given other first-line systemic therapies (p < 0.0001). There were no significant differences in overall survival according to treatment type.

Conclusion

Results from this large US cohort study reflect those obtained in randomized trials of patients with advanced EGFR Mut+ NSCLC and demonstrate their transferability into a real-world setting.

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<![CDATA[A multicenter survey of temporal changes in chemotherapy-induced hair loss in breast cancer patients]]> https://www.researchpad.co/article/5c3fa558d5eed0c484ca346c

Purpose

Many breast cancer patients suffer from chemotherapy-induced hair loss. Accurate information about temporal changes in chemotherapy-induced hair loss is important for supporting patients scheduled to receive chemotherapy, because it helps them to prepare. However, accurate information, on issues such as the frequency of hair loss after chemotherapy, when regrowth starts, the condition of regrown hair, and the frequency of incomplete hair regrowth, is lacking. This study aimed to clarify the long-term temporal changes in chemotherapy-induced hair loss using patient-reported outcomes for chemotherapy-induced hair loss.

Methods

We conducted a multicenter, cross-sectional questionnaire survey. Disease-free patients who had completed adjuvant chemotherapy consisting of anthracycline and/or taxanes for breast cancer within the prior 5 years were enrolled from 47 hospitals and clinics in Japan. Descriptive statistics were obtained in this study. The study is reported according to the STROBE criteria.

Results

The response rate was 81.5% (1511/1853), yielding 1478 questionnaires. Hair loss occurred in 99.9% of patients. The mean time from chemotherapy until hair loss was 18.0 days. Regrowth of scalp hair occurred in 98% of patients. The mean time from the completion of chemotherapy to the beginning of regrowth was 3.3 months. Two years after chemotherapy completion, the scalp-hair recovery rate was <30% in approximately 4% of patients, and this rate showed no improvement 5 years after chemotherapy. Eighty-four percent of the patients initially used wigs, decreasing to 47% by 1 year after chemotherapy and 15.2% after 2 years. The mean period of wig use was 12.5 months. However, a few patients were still using wigs 5 years after completing chemotherapy.

Conclusions

Our survey focused on chemotherapy-induced hair loss in breast cancer patients. We believe these results to be useful for patients scheduled to receive chemotherapy.

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<![CDATA[Assessing the prognostic factors, survival, and recurrence incidence of triple negative breast cancer patients, a single center study in Iran]]> https://www.researchpad.co/article/5c390bd8d5eed0c48491ea0e

Background

Breast cancer is the second leading cause of death due to cancer in women. Triple negative breast cancer (TNBC) is a subgroup with unique behavior. There is a controversy in organ involvement in metastasis. In this study, we planned to define the prognostic factors, survival, and recurrence incidence of patients.

Materials and method

Among the 583 patients with breast mass referred to hematology and oncology clinic in Shariati hospital, Tehran, Iran from March 2005 to March 2015, fifty four patients entered the survival analysis whom we followed for two years until March 2017. Overall survival (OS) and disease-free survival (DFS) and Cumulative recurrence incidences (RI) were estimated. Univariate and multivariate Cox proportional hazards regression was performed to assess risk factors in predicting OS and DFS.

Results

Median follow up for the patients was 5.00 years. The five-year OS, DFS and RI were 86.13% (95% CI (71.42–93.59), 63.09% (95% CI (47.04–75.49) and 32.15% (95% CI (19.52–47.43) respectively. Among the factors studied OS, DFS and RI differed significantly only between patients with and without nodal involvement (P = 0.004, P = 0.003, and P = 0.02 respectively). On the other hand, based on the univariate modeling, patients with nodal involvement had a higher risk of breast cancer-specific death (HR: 17.99, P = 0.004). Furthermore, patients with nodal involvement had a higher risk of breast cancer-specific death or recurrence (HR = 5.64, P = 0.008). In Multivariate model, just the nodal involvement significantly changed the hazard for OS (HR = 23.91, P = 0.001). As the nodal involvement was the only significant risk factor at the 0.2 level of significance, we can consider the hazard ratio of lymph node positivity in DFS univariate models as adjusted hazard.

Conclusion

The only factor with significant effect on OS, DFS and RI was nodal involvement in the pathology report.

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<![CDATA[Borderline-resectable pancreatic adenocarcinoma: Contour irregularity of the venous confluence in pre-operative computed tomography predicts histopathological infiltration]]> https://www.researchpad.co/article/5c3667fcd5eed0c4841a6c6c

Purpose

The purpose of the current study was to compare CT-signs of portal venous confluence infiltration for actual histopathological infiltration of the vein or the tumor/vein interface (TVI) in borderline resectable pancreatic ductal adenocarcinoma (PDAC).

Methods and materials

101 patients with therapy-naïve, primarily resected PDAC of the pancreatic head without arterial involvement were evaluated. The portal venous confluence was assessed for contour irregularity (defined as infiltration) and degree of contact. The sensitivity and specificity of contour irregularity versus tumor to vein contact >180° as well as the combination of the signs for tumor cell infiltration of the vessel wall or TVI was calculated. Overall survival (OS) was compared between groups.

Results

Sensitivity and specificity of contour irregularity for identification of tumor infiltration of the portal venous confluence or the TVI was higher compared to tumor to vessel contact >180° for tumor cell infiltration (96%/79% vs. 91%/38% respectively, p<0.001). The combination of the signs increased specificity to 92% (sensitivity 88%). Patients with contour irregularity/ tumor to vein contact >180°/ both signs had significantly worse overall survival (16.2 vs. 26.5 months/ 17.9 vs. 37.4 months/ 18.5 vs. 26.5 months respectively, all p<0.05).

Conclusion

Portal venous confluence contour irregularity is a strong predictor of actual tumor cell infiltration of the vessel wall or the TVI and should be noted as such in radiological reports.

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<![CDATA[‘A world of competing sorrows’: A mixed methods analysis of media reports of children with cancer abandoning conventional treatment]]> https://www.researchpad.co/article/5c269779d5eed0c48470fa3d

Background

We aimed to provide health practitioners greater insight into the public perception of traditional and complementary medicine (T&CM) use. Our objectives were to identify news media reports of children abandoning conventional treatment for traditional and complementary medicine, analyze the thematic content of these news articles and estimate the tonality portrayed.

Methods

LexisNexis and Factiva were searched for terms related to cancer, children and T&CM. Inclusion criteria were children less than 18 years, in curative phase of treatment who attempted to abandon conventional therapy for any traditional and complementary medicine use. A secondary search was performed in LexisNexis, Factiva and Google News Archive with the names of children in identified cases. Qualitative analysis of news media reports was completed using a grounded theory approach. Quantitative analysis of article sentiment was performed using a linear support vector machine.

Results

Seventeen cases occurring between 2002 and 2016 were included. Five main themes were identified: treatment as torture, power imbalances, rights of parents, evidence versus beliefs and the rights of Indigenous Peoples. Sentiment analysis revealed an overall negative tone, as demonstrated by 73% of the articles.

Interpretation

A better understanding of factors that lead to abandonment of conventional therapy for traditional and complementary medicine as portrayed in the news media may help healthcare providers prevent the occurrence of these cases.

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<![CDATA[Colorectal cancer survival rates in Ghana: A retrospective hospital-based study]]> https://www.researchpad.co/article/5c23f27cd5eed0c484046ef3

Background

Colorectal cancer (CRC) is one of the commonest cancers associated with diverse prognosis times in different parts of the world. Despite medical interventions, the overall clinical outcomes and survival remains very poor for most patients in developing countries. This study therefore investigated the survival rate of colorectal cancer and its prognostic factors among patients at Komfo Anokye Teaching Hospital, Ghana.

Methodology

In this retrospective cohort study, a total of 221 patients diagnosed with CRC from 2009 to 2015 at the Surgical and Oncological units of Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana were employed. The survival graphs were obtained using the Kaplan–Meier method and compared by the Log-rank test. Cox regression analysis was used to assess prognostic factors. All analyses were performed by SPSS version 22.

Results

The median survival time was 15 months 95% CI (11.79–18.21). The overall survival rate for CRC over the 5 years period was 16.0%. The survival rates at the 1st, 2nd, 3rd, 4th and 5th years were 64% 95% CI (56.2–71.1), 40% 95% CI (32.2–50.1), 21% 95% CI (11.4–30.6) 16% 95% CI (8.9–26.9) and 16% 95% CI (7.3–24.9). There was a significant difference in the survival rate of colorectal cancer according to the different stages (p = 0.0001). Family history [HR = (3.44), p = 0.029)], Chemotherapy [HR = (0.23), p = <0.0001)], BMI [HR = (1.78), p = 0.017)] and both chemo/radiotherapy (HR = (3.63), p = 0.042)] were the significant social and clinical factors influencing the overall survival. Pathological factors such as TNM tumour stage (p = 0.012), depth of tumour invasion (p = 0.036), lymph node metastasis (p = 0.0001), and distance metastasis (p = 0.001) were significantly associated with overall survival.

Conclusion

The study has clearly demonstrated that survival rate for CRC patients at KATH, Ghana is very low in a 5 years period. This is influenced by significant number of clinical and pathological prognostic factors. Identification of prognostic factors would be a primary basis for early prediction and treatment of patients with colorectal cancer.

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<![CDATA[Human equilibrative nucleoside transporter 1 (hENT1) expression as a predictive biomarker for gemcitabine chemotherapy in biliary tract cancer]]> https://www.researchpad.co/article/5c215134d5eed0c4843f9262

Gemcitabine is a principal chemotherapeutic agent for biliary tract cancer (BTC). Expression of human equilibrative nucleoside transporter 1 (hENT1) is regarded as a potential predictive biomarker for a gemcitabine response in some cancers. This study was conducted to investigate the association between hENT1 expression and the effects of gemcitabine on BTC cell lines and on patients with advanced BTC receiving gemcitabine-based chemotherapy. A total of four BTC cell lines, HuCCT1, SNU-478, SNU-1079, and SNU-1196, were tested. mRNA and protein expression levels of hENT1 were measured by quantitative reverse-transcription polymerase chain reaction and western blotting, respectively. Cell viability after gemcitabine treatment was measured in a chemosensitivity assay. For clinical assessment, 40 patients with unresectable or recurrent BTC who were treated with gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) between June 2012 and May 2014 were enrolled. Among the four cell lines, SNU1196 showed the highest mRNA and protein levels of hENT1. Expression of hENT1 showed a linear correlation with the log value of the half-maximal inhibitory concentration of gemcitabine. During incubation with gemcitabine, pretreatment with hENT1-specific small interfering RNA (siRNA) resulted in higher cell viability than that in samples pretreated with control siRNA. In a clinical evaluation, the median progression-free survival was 24 and 11 weeks among patients with strong and weak intratumoral hENT1 immunohistochemical staining (P = 0.05), and the median overall survival was 52 and 26 weeks (P = 0.15), respectively. In conclusion, this study showed that increased hENT1 expression is associated with a stronger toxic effect of gemcitabine on BTC cell lines. The clinical outcomes in this study suggest that increased intratumoral hENT1 immunohistochemical staining is a possible biomarker predicting better therapeutic effects of gemcitabine on patients with advanced BTC. Further studies are needed to determine the precise role of hENT1 in BTC.

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<![CDATA[Gender as an independent prognostic factor in small-cell lung cancer: Inha Lung Cancer Cohort study using propensity score matching]]> https://www.researchpad.co/article/5c1966cdd5eed0c484b52ed9

Introduction

The prognostic relevance of gender is undetermined in patients with small-cell lung cancer (SCLC). Therefore, we investigated whether gender is a prognostic factor in a SCLC cohort after controlling for confounding factors.

Materials and methods

Fifteen prognostic factors were classified into four groups (patient, stage migration, tumor, and treatment). The prognostic relevance of gender was evaluated using propensity score matching, Cox proportional hazards regression, and stepwise fashion adjustments.

Results

Of 591 patients with SCLC, 88 were women (14.9%). Women were more likely than men to have no history of smoking (48.9% vs. 2.0%, P < 0.001) and limited disease (48.9% vs. 37.8%, P = 0.050). Women had less progressive disease in M stage than men (52.3% vs. 62.8%, P = 0.031). Women had better survival than men in the entire cohort (median survival times [MSTs] and 95% confidence intervals [CIs]: 9.7 months and 7.8–11.6 for women, 8.0 months and 7.0–8.9 for men, log-rank P = 0.034) and in the matched cohort (MSTs and 95% CIs: 8.8 months and 5.8–11.8 for women, 5.9 months and 4.5–7.4 for men, log-rank P = 0.013). Female gender was a prognostic factor predicting better survival, even after stepwise and full adjustment with all prognostic variables (adjusted hazard ratios and 95% CIs: 0.51 and 0.34–0.77, P = 0.001 for entire cohort, 0.42 and 0.24–0.75, P = 0.003 for matched cohort).

Conclusions

Our results confirmed that gender is an independent prognostic factor in patients with SCLC.

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