ResearchPad - clinical-oncology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Factors associated with the job satisfaction of certified nurses and nurse specialists in cancer care in Japan: Analysis based on the Basic Plan to Promote Cancer Control Programs]]> https://www.researchpad.co/article/elastic_article_15727 As the Japanese population ages, the number of cancer patients will likely increase. Therefore, qualified cancer health care providers should be recruited and retained. Nurse job satisfaction is influenced by numerous factors and may affect staff turnover and patient outcomes.ObjectivesTo evaluate the job satisfaction of certified nurses and nurse specialists in Japanese cancer care and elucidate factors associated with job satisfaction.MethodsParticipants in this cross-sectional study comprised 200 certified nurse specialists and 1,472 certified nurses working in Japanese cancer care. A chi-square test and logistic regression analysis were conducted to identify job satisfaction factors.ResultsJob satisfaction was present in 38.45% and 49.00% of certified nurses and nurse specialists, respectively. Certified nurses associated job satisfaction with cross-departmental activities (OR 2.24, p<0.001), positive evaluation from senior stuff (OR 4.58, p<0.001), appropriate staff allocation (OR 1.75, p<0.001), more than five years certified nurse experience (OR 1.91, p<0.001), and positive evaluation of the development of certified nurses (OR 2.13, p<0.01) and nurse specialists (OR 1.37, p<0.05). Low job satisfaction was associated with working on a ward (OR 0.51, p<0.001) and a capacity of more than 200 beds (OR 0.33, p = 0.00). Certified nurse specialists associated job satisfaction with palliative care team participation (OR 2.64, p<0.05), cross–sectional activities (OR 7.06, p<0.01), positive evaluation from senior stuff (OR 13.15, p<0.001), presence of certified nurses in radiation therapy (OR 2.91, p<0.05), positive certified nurse specialist development evaluation (OR 7.35, p<0.001), medical service fees (OR 3.78, p<0.01), and independent activities (OR 11.34, p<0.01).ConclusionsWe identified factors related to activities, facilities, and the cancer care team associated with job satisfaction of certified nurses and nurse specialists in Japanese cancer care. Suggestions are provided to enhance job satisfaction through Japan’s Basic Plan to Promote Cancer Control, which may help hospital administrators retain nursing staff. ]]> <![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.

]]>
<![CDATA[Radioimmunotherapy of methicillin-resistant <i>Staphylococcus aureus</i> in planktonic state and biofilms]]> https://www.researchpad.co/article/elastic_article_14628 Implant associated infections such as periprosthetic joint infections are difficult to treat as the bacteria form a biofilm on the prosthetic material. This biofilm complicates surgical and antibiotic treatment. With rising antibiotic resistance, alternative treatment options are needed to treat these infections in the future. The aim of this article is to provide proof-of-principle data required for further development of radioimmunotherapy for non-invasive treatment of implant associated infections.MethodsPlanktonic cells and biofilms of Methicillin-resistant staphylococcus aureus are grown and treated with radioimmunotherapy. The monoclonal antibodies used, target wall teichoic acids that are cell and biofilm specific. Three different radionuclides in different doses were used. Viability and metabolic activity of the bacterial cells and biofilms were measured by CFU dilution and XTT reduction.ResultsAlpha-RIT with Bismuth-213 showed significant and dose dependent killing in both planktonic MRSA and biofilm. When planktonic bacteria were treated with 370 kBq of 213Bi-RIT 99% of the bacteria were killed. Complete killing of the bacteria in the biofilm was seen at 185 kBq. Beta-RIT with Lutetium-177 and Actinium-225 showed little to no significant killing.ConclusionOur results demonstrate the ability of specific antibodies loaded with an alpha-emitter Bismuth-213 to selectively kill staphylococcus aureus cells in vitro in both planktonic and biofilm state. RIT could therefore be a potentially alternative treatment modality against planktonic and biofilm-related microbial infections. ]]> <![CDATA[Prevalence of endosalpingiosis and other benign gynecologic lesions]]> https://www.researchpad.co/article/elastic_article_14492 Endosalpingiosis, traditionally regarded as an incidental pathological finding, was recently reported to have an association with gynecologic malignancies. To determine the prevalence of endosalpingiosis, we evaluated all benign appearing adnexal lesions using the Sectioning and Extensively Examining-Fimbria (SEE-Fim) protocol, and queried the pathology database for the presence of endosalpingiosis, gynecologic malignancy, endometriosis, Walthard nests, and paratubal cysts. Using the SEE-Fim protocol, the prevalence of endosalpingiosis, endometriosis, Walthard nests, and paratubal cysts were 22%, 45%, 33%, and 42% respectively, substantially higher than previously reported. All lesions were observed to increase with age except endometriosis which increased until menopause then decreased dramatically. Among specimens including ovarian tissue, the prevalence of implantation of at least one lesion type was ubiquitous in patients age 51 and older (93%). The clinical significance of endosalpingiosis should be a continued area of research with larger trials assessing prevalence, factors affecting incidence, and association with malignancy. Our findings contribute to elucidating the origin of ectopic lesions and gynecologic disease risk.

]]>
<![CDATA[Early budget impact analysis on magnetic seed localization for non-palpable breast cancer surgery]]> https://www.researchpad.co/article/elastic_article_13866 Current localization techniques used in breast conserving surgery for non-palpable tumors show several disadvantages. Magnetic Seed Localization (MSL) is an innovative localization technique aiming to overcome these disadvantages. This study evaluated the expected budget impact of adopting MSL compared to standard of care.MethodsStandard of care with Wire-Guided Localization (WGL) and Radioactive Seed Localization (RSL) use was compared with a future situation gradually adopting MSL next to RSL or WGL from a Dutch national perspective over 5 years (2017–2022). The intervention costs for WGL, RSL and MSL and the implementation costs for RSL and MSL were evaluated using activity-based costing in eight Dutch hospitals. Based on available list prices the price of the magnetic seed was ranged €100-€500.ResultsThe intervention costs for WGL, RSL and MSL were respectively: €2,617, €2,834 and €2,662 per patient and implementation costs were €2,974 and €26,826 for MSL and RSL respectively. For standard of care the budget impact increased from €14.7m to €16.9m. Inclusion of MSL with a seed price of €100 showed a budget impact of €16.7m. Above a price of €178 the budget impact increased for adoption of MSL, rising to €17.6m when priced at €500.ConclusionMSL could be a cost-efficient localization technique in resecting non-palpable tumors in the Netherlands. The online calculation model can inform adoption decisions internationally. When determining retail price of the magnetic seed, cost-effectiveness should be considered. ]]> <![CDATA[Role of intraoperative oliguria in risk stratification for postoperative acute kidney injury in patients undergoing colorectal surgery with an enhanced recovery protocol: A propensity score matching analysis]]> https://www.researchpad.co/article/N90678846-11a4-456d-84dc-7e3677d2f27e

Background

The enhanced recovery after surgery (ERAS) protocol for colorectal cancer resection recommends balanced perioperative fluid therapy. According to recent guidelines, zero-balance fluid therapy is recommended in low-risk patients, and immediate correction of low urine output during surgery is discouraged. However, several reports have indicated an association of intraoperative oliguria with postoperative acute kidney injury (AKI). We investigated the impact of intraoperative oliguria in the colorectal ERAS setting on the incidence of postoperative AKI.

Patients and methods

From January 2017 to August 2019, a total of 453 patients underwent laparoscopic colorectal cancer resection with the ERAS protocol. Among them, 125 patients met the criteria for oliguria and were propensity score (PS) matched to 328 patients without intraoperative oliguria. After PS matching had been performed, 125 patients from each group were selected and the incidences of AKI were compared between the two groups. Postoperative kidney function and surgical outcomes were also evaluated.

Results

The incidence of AKI was significantly higher in the intraoperative oliguria group than in the non-intraoperative oliguria group (26.4% vs. 11.2%, respectively, P = 0.002). Also, the eGFR reduction on postoperative day 0 was significantly greater in the intraoperative oliguria than non-intraoperative oliguria group (−9.02 vs. −1.24 mL/min/1.73 m2 respectively, P < 0.001). In addition, the surgical complication rate was higher in the intraoperative oliguria group than in the non-intraoperative oliguria group (18.4% vs. 9.6%, respectively, P = 0.045).

Conclusions

Despite the proven benefits of perioperative care with the ERAS protocol, caution is required in patients with intraoperative oliguria to prevent postoperative AKI. Further studies regarding appropriate management of intraoperative oliguria in association with long-term prognosis are needed in the colorectal ERAS setting.

]]>
<![CDATA[Distinguishing moral hazard from access for high-cost healthcare under insurance]]> https://www.researchpad.co/article/N9aa1c21e-eb0c-47d9-9336-743c9eef5b98

Context

Health policy has long been preoccupied with the problem that health insurance stimulates spending (“moral hazard”). However, much health spending is costly healthcare that uninsured individuals could not otherwise access. Field studies comparing those with more or less insurance cannot disaggregate moral hazard versus access. Moreover, studies of patients consuming routine low-dollar healthcare are not informative for the high-dollar healthcare that drives most of aggregate healthcare spending in the United States.

Methods

We test indemnities as an alternative theory-driven counterfactual. Such conditional cash transfers would maintain an opportunity cost for patients, unlike standard insurance, but also guarantee access to the care. Since indemnities do not exist in U.S. healthcare, we fielded two blinded vignette-based survey experiments with 3,000 respondents, randomized to eight clinical vignettes and three insurance types. Our replication uses a population that is weighted to national demographics on three dimensions.

Findings

Most or all of the spending due to insurance would occur even under an indemnity. The waste attributable to moral hazard is undetectable.

Conclusions

For high-cost care, policymakers should be more concerned about the foregone efficient spending for those lacking full insurance, rather than the wasteful spending that occurs with full insurance.

]]>
<![CDATA[Risk of stomach cancer incidence in a cohort of Mayak PA workers occupationally exposed to ionizing radiation]]> https://www.researchpad.co/article/Nb5246167-3f67-43a4-8a84-93c6a22ed7ff

Stomach cancer is a widespread health condition associated with environmental and genetic factors. Contribution of ionizing radiation to stomach cancer etiology is not sufficiently studied. This study was aimed to assess an association of the stomach cancer incidence risk with doses from occupational radiation exposure in a cohort of workers hired at main Mayak production association facilities in 1948–1982 taking into account non-radiation factors including digestive disorders. The study cohort comprised 22,377 individuals and by 31.12.2013 343 stomach cancer diagnoses had been reported among the cohort members. Occupational stomach absorbed doses were provided by the Mayak Worker Dosimetry System– 2008 (MWDS–2008) for external gamma ray exposure and by the Mayak Worker Dosimetry System– 2013 (MWDS–2013) for internal exposure to plutonium. Excess relative risks (ERR) per Gy for stomach cancer were estimated using the Poisson’s regression. Analyses were run using the AMFIT module of the EPICURE software. The stomach cancer incidence risk in the study cohort was found to be significantly associated with the stomach absorbed dose of gamma rays: ERR/Gy = 0.19 (95% CI: 0.01, 0.44) with a 0 year lag, and ERR/Gy = 0.20 (95% CI: 0.01, 0.45) with a 5 year lag. To estimate the baseline risk, sex, attained age, smoking status and alcohol consumption, chronic diseases (peptic ulcer, gastritis and duodenitis) were taken into account. No modifications of the radiogenic risk by non-radiation factors were found in the study worker cohort. No association of the stomach cancer incidence risk with internal exposure to incorporated plutonium was observed.

]]>
<![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.

]]>
<![CDATA[Clinical course and end-of-life care in patients who have died after allogeneic stem cell transplantation]]> https://www.researchpad.co/article/Ne16ebf33-17ff-432e-842f-3ecd19ef8571

Purpose

Allogeneic stem cell transplantation may cure approximately 50% of patients, however, a significant part of the other half might benefit from a high-quality palliative care medicine at the end of life. Somatic, psychic and spiritual needs of these patients may differ from those of patients suffering from incurable solid tumours and are not comprehensively evaluated so far.

Methods

To address this question, data from charts of 123 patients who have died after allogeneic stem cell transplantation were extracted. In detail, the time line of the clinical course, the symptoms, the administered drugs and other applied procedures were analysed.

Results

Approximately one half of the patients, who have died after stem cell transplantation, did not live more than 5 months. Two-thirds of patients died within 14 months after SCT. 28.5% of the patients could not be discharged after transplantation. However, a significant proportion had a low ECOG-score (0–1) prior to death, indicating a high degree of mobility. Major symptoms were weakness, fatigue and need for aid at daily activities. Severe pain, dyspnoea and obstipation, as known from patients suffering from advanced solid tumours, were rare. In consequence, use of opioids seemed to be less frequent than in patients with solid tumours. Measures of intensive care and i.v.-drug administration were applied to a significant proportion of patients.

Conclusion

The present investigation indicates that the somatic, psychic and spiritual end-of-life-care after allogeneic stem cell transplantation could be optimised. A significant problem for the transplantation team seems to be the realisation of necessity to switch the curative concept into a palliative ambition. Requirements are a subsequent prospectively conducted investigation and an intensification of cooperation between transplant and palliative care teams.

]]>
<![CDATA[Transcriptome analysis reveals overlap in fusion genes in a phase I clinical cohort of TNBC and HGSOC patients treated with buparlisib and olaparib]]> https://www.researchpad.co/article/N896ea1b1-0f3c-4bd9-a967-c2c651f06daf

Purpose

Fusion genes can be therapeutically relevant if they result in constitutive activation of oncogenes or repression of tumor suppressors. However, the prevalence and role of fusion genes in female cancers remain largely unexplored. Here, we investigate the fusion gene landscape in triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC), two subtypes of female cancers with high molecular similarity but limited treatment options at present.

Methods

RNA-seq was utilized to identify fusion genes in a cohort of 18 TNBC and HGSOC patients treated with the PI3K inhibitor buparlisib and the PARP inhibitor olaparib in a phase I clinical trial (NCT01623349). Differential gene expression analysis was performed to assess the function of fusion genes in silico. Finally, these findings were correlated with the reported clinical outcomes.

Results

A total of 156 fusion genes was detected, whereof 44/156 (28%) events occurred in more than one patient. Low recurrence across samples indicated that the majority of fusion genes were private passenger events. The long non-coding RNA MALAT1 was involved in 97/156 (62%) fusion genes, followed in prevalence by MUC16, FOXP1, WWOX and XIST. Gene expression of FOXP1 was significantly elevated in patients with vs. without FOXP1 fusion (P= 0.02). From a clinical perspective, FOXP1 fusions were associated with a favorable overall survival.

Conclusions

In summary, this study provides the first characterization of fusion genes in a cohort of TNBC and HGSOC patients. An improved mechanistic understanding of fusion genes will support the future identification of innovative therapeutic approaches for these challenging diseases.

Electronic supplementary material

The online version of this article (10.1007/s00432-019-03078-9) contains supplementary material, which is available to authorized users.

]]>
<![CDATA[Tissue factor activity on microvesicles from cancer patients]]> https://www.researchpad.co/article/Naba2fc50-61f7-41b1-8de2-9907408477a2

Purpose

The expression of active tissue factor (TF) on the surface of microvesicles (MVs) is essential for the activation of the coagulation system and transduction of the signaling pathways in cancer cells. In its use as a biomarker for cancer-associated venous thromboembolism (VTE), TF has shown high expression variability. As a contribution to this discussion, we present a study investigating plasma samples from patients with various progressive tumors at high risk for VTE.

Methods

Based on our previous study uncovering microvesicles (MVs), the larger ectosome-like extracellular vesicles (EV), as the major source of TF activity in EV preparations, we now determined TF activity on enriched MVs isolated from plasma of cancer patients and compared it with that on MVs from healthy individuals.

Results

We found considerably higher amounts of MVs as well as higher levels of MV-bound TF activities in the plasma of cancer patients. We also show that preparations from plasma of cancer patients have the potency to induce ERK phosphorylation in a human tumor cell line through proteinase-activated receptor two (PAR2) activation.

Conclusion

We suggest that MVs instead of whole EV preparations, and TF activity rather than its antigenic quantification should be used in clinical studies for identifying patients with progressive tumors at high risk for VTE.

Graphic abstract

Electronic supplementary material

The online version of this article (10.1007/s00432-019-03073-0) contains supplementary material, which is available to authorized users.

]]>
<![CDATA[Precision oncotherapy based on liquid biopsies in multidisciplinary treatment of unresectable recurrent rectal cancer: a retrospective cohort study]]> https://www.researchpad.co/article/N4c8d4220-52cd-461e-971a-3cea3b3bc780

Background

Third line innovative systemic treatments and loco-regional chemotherapy by hypoxic pelvic perfusion (HPP) have both been proposed for the treatment of unresectable not responsive recurrent rectal cancer (URRC). In the present study, we have compared the safety and efficacy of HPP/target therapy, using drug regimens selected by liquid biopsy precision oncotherapy, to third-line systemic therapy based on tissue specimens precision oncotherapy.

Methods

HPP/target therapy regimens were selected based on precision oncotherapy, including assays for chemosensitivity and viability, and qRT-PCR for tumor-related gene expression. In the control group, systemic third-line and further lines of therapy were defined according to clinical and biological parameters.

Results

From 2007 to 2019, 62 URRC patients were enrolled, comprised of 43 patients in the HPP/target-therapy group and 19 patients in the systemic therapy control group. No HPP related complications were reported and the most common adverse events were skin and bone marrow toxicity. In the HPP/target-therapy group, the ORR was 41.8% whereas in the systemic therapy control group was 15.8%. DCR of the HPP/target-therapy group was significantly improved over the systemic therapy group (P = 0.001), associated with a PFS of 8 vs 4 months (P = 0.009), and OS of 20 vs 8 months (P = 0.046).

Conclusions

The present data indicate that in URCC patients, the integration of HPP/target-therapy and precision oncotherapy based upon liquid biopsy is as effective and efficacious as third-line treatment in local disease control and, therefore, deserves to be further assessed and compared to conventional systemic treatments in future prospective randomized trials.

]]>
<![CDATA[Validation of risk factors for recurrence of renal cell carcinoma: Results from a large single-institution series]]> https://www.researchpad.co/article/Ne7ebe4b8-b927-4fd1-a438-3fd04efc5df6

Purpose

To validate prognostic factors and determine the impact of obesity, hypertension, smoking and diabetes mellitus (DM) on risk of recurrence after surgery in patients with localized renal cell carcinoma (RCC).

Materials and methods

We performed a retrospective cohort study among patients that underwent partial or radical nephrectomy at Weill Cornell Medicine for RCC and collected preoperative information on RCC risk factors, as well as pathological data. Cases were reviewed for radiographic evidence of RCC recurrence. A Cox proportional-hazards model was developed to determine the contribution of RCC risk factors to recurrence risk. Disease-free survival and overall survival were analyzed using the Kaplan-Meier method and log-rank test.

Results

We identified 873 patients who underwent surgery for RCC between the years 2000–2015. In total 115 patients (13.2%) experienced a disease recurrence after a median follow up of 4.9 years. In multivariate analysis, increasing pathological T-stage (HR 1.429, 95% CI 1.265–1.614) and Nuclear grade (HR 2.376, 95% CI 1.734–3.255) were independently associated with RCC recurrence. In patients with T1-2 tumors, DM was identified as an additional independent risk factor for RCC recurrence (HR 2.744, 95% CI 1.343–5.605). Patients with DM had a significantly shorter median disease-free survival (1.5 years versus 2.6 years, p = 0.004), as well as median overall survival (4.1 years, versus 5.8 years, p<0.001).

Conclusions

We validated high pathological T-stage and nuclear grade as independent risk factors for RCC recurrence following nephrectomy. DM is associated with an increased risk of recurrence among patients with early stage disease.

]]>
<![CDATA[Exploit fully automatic low-level segmented PET data for training high-level deep learning algorithms for the corresponding CT data]]> https://www.researchpad.co/article/5c8823d0d5eed0c484639091

We present an approach for fully automatic urinary bladder segmentation in CT images with artificial neural networks in this study. Automatic medical image analysis has become an invaluable tool in the different treatment stages of diseases. Especially medical image segmentation plays a vital role, since segmentation is often the initial step in an image analysis pipeline. Since deep neural networks have made a large impact on the field of image processing in the past years, we use two different deep learning architectures to segment the urinary bladder. Both of these architectures are based on pre-trained classification networks that are adapted to perform semantic segmentation. Since deep neural networks require a large amount of training data, specifically images and corresponding ground truth labels, we furthermore propose a method to generate such a suitable training data set from Positron Emission Tomography/Computed Tomography image data. This is done by applying thresholding to the Positron Emission Tomography data for obtaining a ground truth and by utilizing data augmentation to enlarge the dataset. In this study, we discuss the influence of data augmentation on the segmentation results, and compare and evaluate the proposed architectures in terms of qualitative and quantitative segmentation performance. The results presented in this study allow concluding that deep neural networks can be considered a promising approach to segment the urinary bladder in CT images.

]]>
<![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.

]]>
<![CDATA[Real-time adaptive planning method for radiotherapy treatment delivery for prostate cancer patients, based on a library of plans accounting for possible anatomy configuration changes]]> https://www.researchpad.co/article/5c818e8ad5eed0c484cc24c8

Background and purpose

In prostate cancer treatment with external beam radiation therapy (EBRT), prostate motion and internal changes in tissue distribution can lead to a decrease in plan quality. In most currently used planning methods, the uncertainties due to prostate motion are compensated by irradiating a larger treatment volume. However, this could cause underdosage of the treatment volume and overdosage of the organs at risk (OARs). To reduce this problem, in this proof of principle study we developed and evaluated a novel adaptive planning method. The strategy proposed corrects the dose delivered by each beam according to the actual position of the target in order to produce a final dose distribution dosimetrically as similar as possible to the prescribed one.

Material and methods

Our adaptive planning method was tested on a phantom case and on a clinical case. For the first, a pilot study was performed on an in-silico pelvic phantom. A “library” of intensity modulated RT (IMRT) plans corresponding to possible positions of the prostate during a treatment fraction was generated at planning stage. Then a 3D random walk model was used to simulate possible displacements of the prostate during the treatment fraction. At treatment stage, at the end of each beam, based on the current position of the target, the beam from the library of plans, which could reproduce the best approximation of the prescribed dose distribution, was selected and delivered. In the clinical case, the same approach was used on two prostate cancer patients: for the first a tissue deformation was simulated in-silico and for the second a cone beam CT (CBCT) taken during the treatment was used to simulate an intra-fraction change. Then, dosimetric comparisons with the standard treatment plan and, for the second patient, also with an isocenter shift correction, were performed.

Results

For the phantom case, the plan generated using the adaptive planning method was able to meet all the dosimetric requirements and to correct for a misdosage of 13% of the dose prescription on the prostate. For the first clinical case, the standard planning method caused underdosage of the seminal vesicles, respectively by 5% and 4% of the prescribed dose, when the position changes for the target were correctly taken into account. The proposed adaptive planning method corrected any possible missed target coverage, reducing at the same time the dose on the OARs. For the second clinical case, both with the standard planning strategy and with the isocenter shift correction target coverage was significantly worsened (in particular uniformity) and some organs exceeded some toxicity objectives. While with our approach, the most uniform coverage for the target was produced and systematically the lowest toxicity values for the organs at risk were achieved.

Conclusions

In our proof of principle study, the adaptive planning method performed better than the standard planning and the isocenter shift methods for prostate EBRT. It improved the coverage of the treatment volumes and lowered the dose to the OARs. This planning method is particularly promising for hypofractionated IMRT treatments in which a higher precision and control on dose deposition are needed. Further studies will be performed to test more extensively the proposed adaptive planning method and to evaluate it at a full clinical level.

]]>
<![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

]]>
<![CDATA[Highly efficient and sensitive patient-specific quality assurance for spot-scanned proton therapy]]> https://www.researchpad.co/article/5c6f1505d5eed0c48467acb1

The purpose of this work was to develop an end-to-end patient-specific quality assurance (QA) technique for spot-scanned proton therapy that is more sensitive and efficient than traditional approaches. The patient-specific methodology relies on independently verifying the accuracy of the delivered proton fluence and the dose calculation in the heterogeneous patient volume. A Monte Carlo dose calculation engine, which was developed in-house, recalculates a planned dose distribution on the patient CT data set to verify the dose distribution represented by the treatment planning system. The plan is then delivered in a pre-treatment setting and logs of spot position and dose monitors, which are integrated into the treatment nozzle, are recorded. A computational routine compares the delivery log to the DICOM spot map used by the Monte Carlo calculation to ensure that the delivered parameters at the machine match the calculated plan. Measurements of dose planes using independent detector arrays, which historically are the standard approach to patient-specific QA, are not performed for every patient. The nozzle-integrated detectors are rigorously validated using independent detectors in regular QA intervals. The measured data are compared to the expected delivery patterns. The dose monitor reading deviations are reported in a histogram, while the spot position discrepancies are plotted vs. spot number to facilitate independent analysis of both random and systematic deviations. Action thresholds are linked to accuracy of the commissioned delivery system. Even when plan delivery is acceptable, the Monte Carlo second check system has identified dose calculation issues which would not have been illuminated using traditional, phantom-based measurement techniques. The efficiency and sensitivity of our patient-specific QA program has been improved by implementing a procedure which independently verifies patient dose calculation accuracy and plan delivery fidelity. Such an approach to QA requires holistic integration and maintenance of patient-specific and patient-independent QA.

]]>
<![CDATA[Haralick texture feature analysis for quantifying radiation response heterogeneity in murine models observed using Raman spectroscopic mapping]]> https://www.researchpad.co/article/5c706766d5eed0c4847c6fbd

Tumour heterogeneity plays a large role in the response of tumour tissues to radiation therapy. Inherent biological, physical, and even dose deposition heterogeneity all play a role in the resultant observed response. We here implement the use of Haralick textural analysis to quantify the observed glycogen production response, as observed via Raman spectroscopic mapping, of tumours irradiated within a murine model. While an array of over 20 Haralick features have been proposed, we here concentrate on five of the most prominent features: homogeneity, local homogeneity, contrast, entropy, and correlation. We show that these Haralick features can be used to quantify the inherent heterogeneity of the Raman spectroscopic maps of tumour response to radiation. Furthermore, our results indicate that Haralick-calculated textural features show a statistically significant dose dependent variation in response heterogeneity, specifically, in glycogen production in tumours irradiated with clinically relevant doses of ionizing radiation. These results indicate that Haralick textural analysis provides a quantitative methodology for understanding the response of murine tumours to radiation therapy. Future work in this area can, for example, utilize the Haralick textural features for understanding the heterogeneity of radiation response as measured by biopsied patient tumour samples, which remains the standard of patient tumour investigation.

]]>