The consequence of cardiac substructure irradiation in patients receiving stereotactic body radiation therapy (SBRT) is not well characterized. We reviewed the charts of patients with central lung ...tumors managed by definitive SBRT from June 2010-April 2019. All patients were treated with five fractions, typically either 5000 cGy (44.6%) or 5500 cGy (42.2%). Via a multi-patient atlas, fourteen cardiac substructures were autosegmented, manually reviewed and analyzed using dosimetric parameters. A total of 83 patients were included with a median follow up of 33.4 months. Univariate Cox regression analysis identified a D45% dose to the right atria and ventricle for further study. Sequential log-rank testing evaluating an association between non-cancer associated survival and D45% dose to the right atria or ventricle and association was employed, identifying candidate cutoff values of 890.3 cGy and 564.4 cGy, respectively. Kaplan-Meier analysis using the reported cutoff values found the D45% right atria constraint to be significantly associated with non-cancer associated (
≤ 0.001) and overall survival (
≤ 0.001) but not the right ventricle constraint. Within a multivariate model, the proposed right atria D45% cutoff remained significantly correlated with non-cancer associated survival (Hazard's Ratio (HR) ≤ 8.5, 95% confidence interval (CI) 1.1-64.5,
≤ 0.04) and OS (HR ≤ 6.1, 95% CI 1.0-36.8,
≤ 0.04). In conclusion, a dose to D45% of the right atria significantly correlated with outcome and the candidate constraint of 890 cGy stratified non-cancer associated and OS. The inclusion of these findings with previously characterized relationships between proximal airway constraints and survival enhances our understanding of why centrally located tumors are high risk and potentially identifies key constraints in organ at risk prioritization.
(ProQuest: ... denotes formulae and/or non-USASCII text omitted; see image) Let R be a commutative Noetherian ring that is a smooth ...-algebra. For each ideal ... of R and integer k, we prove that ...the local cohomology module ... has finitely many associated prime ideals. This settles a crucial outstanding case of a conjecture of Lyubeznik asserting this finiteness for local cohomology modules of all regular rings.PUBLICATION ABSTRACT
The role of prophylactic high-dose gabapentin for the management of oral mucositis during radiation therapy for head and neck squamous cell carcinoma (HNSCC) remains controversial.
A retrospective ...cohort analysis was performed on primary HNSCC patients treated at our institution. Kruskal-Wallis and Fisher's exact tests were used to compare the patients' baseline characteristics. Multivariate competing risk and logistic regressions were performed to evaluate time to first opioid use and feeding tube placement.
In total, 480 consecutive HNSCC patients were included. Within this cohort, 186 patients received 3600 mg gabapentin, 182 received 300 to 3200 mg gabapentin, and 112 received no gabapentin. The time to first opioid use was greater in the 3600 mg group compared with the no gabapentin group (34.3 vs. 23.9 days,
< 0.001) and to the 300 to 3200 mg group (28.0 days,
< 0.001). The proportion of patients requiring opioids at any point during RT was lower in the 3600 mg gabapentin group compared with the no gabapentin group (31.8% vs. 60.1%,
< 0.001) and with the 300 to 3200 mg group (63.8%,
< 0.001).
Prophylactic use of 3600 mg gabapentin was well tolerated, halved overall opioid use, and delayed the time to first opioid use during radiation therapy.
Nicotine and lung cancer Warren, Graham; Singh, Anurag
Journal of carcinogenesis,
01/2013, Letnik:
12, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Tobacco use in cancer patients is associated with increased cancer treatment failure and decreased survival. Nicotine is one of over 7,000 compounds in tobacco smoke and nicotine is the principal ...chemical associated with addiction. The purpose of this article is to review the tumor promoting activities of nicotine. Nicotine and its metabolites can promote tumor growth through increased proliferation, angiogenesis, migration, invasion, epithelial to mesenchymal transition, and stimulation of autocrine loops associated with tumor growth. Furthermore, nicotine can decrease the biologic effectiveness of conventional cancer treatments such as chemotherapy and radiotherapy. Common mechanisms appear to involve activation of nicotinic acetylcholine receptors and beta-adrenergic receptors leading to downstream activation of parallel signal transduction pathways that facilitate tumor progression and resistance to treatment. Data suggest that nicotine may be an important mechanism by which tobacco promotes tumor development, progression, and resistance to cancer treatment.
Purpose
To evaluate the association of various gene expression assays with pathologic complete response (pCR) in the setting of neoadjuvant chemotherapy among patients with breast cancer
Methods
The ...National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with stage I-III breast cancer who underwent neoadjuvant chemotherapy and either 21-gene recurrence score (RS) or 70-gene signature (GS). Logistic multivariable analysis (MVA) was performed to identify variables associated with pCR.
Results
A total of 3009 patients met our inclusion criteria. The median follow up was 48.0 months (interquartile range 32.2–66.7 months). On logistic MVA for all patients, those with a high risk from GS (adjusted odds ratio aOR 3.23, 95% confidence interval CI 1.49–8.13,
p
= 0.006) or with RS ≥ 31 (aOR 1.99, 95% CI 1.41–2.82,
p
< 0.001) were more likely to have pCR. When compared to RS ≥ 31, a high risk from GS was not associated with pCR (aOR 1.01, 95% CI 0.75–1.37,
p
= 0.94). However, among those with favorable hormone receptor status, similar findings were noted, except that those with a high risk group from GS were less likely to have pCR compared to those with RS ≥ 31 (aOR 0.65, 95% CI 0.43–0.96,
p
= 0.03). When analyses were repeated using a high risk group from RS defined as RS ≥ 26 among those with favorable hormone receptor status, RS ≥ 26 was not associated with pCR when compared to the high risk from GS (aOR 0.74, 0.50–1.07,
p
= 0.12).
Conclusions
To our knowledge, this is the largest study using a nationwide oncology database suggesting that high recurrence risk groups in both assays were associated with pCR. Among those with favorable hormone receptor status, RS ≥ 31 may be a more selective prognostic marker for pCR.
Let
X
be a closed equidimensional local complete intersection subscheme of a smooth projective scheme
Y
over a field, and let
X
t
denote the
t
-th thickening of
X
in
Y
. Fix an ample line bundle
O
Y
...(
1
)
on
Y
. We prove the following asymptotic formulation of the Kodaira vanishing theorem: there exists an integer
c
, such that for all integers
t
⩾
1
, the cohomology group
H
k
(
X
t
,
O
X
t
(
j
)
)
vanishes for
k
<
dim
X
and
j
<
-
c
t
. Note that there are no restrictions on the characteristic of the field, or on the singular locus of
X
. We also construct examples illustrating that a linear bound is indeed the best possible, and that the constant
c
is unbounded, even in a fixed dimension.
Abstract Background Nivestym, a biosimilar granulocyte colony‐stimulating factor (G‐CSF) to the originator filgrastim (Neupogen), is now being used for the mobilization of peripheral blood stem cells ...(PBSC) in allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We aim to compare the efficacy of Nivestym and Neupogen for PBSC mobilization in healthy allogeneic donors. Methods We conducted a retrospective single‐center study including 541 adult allo‐HSCT donors receiving Nivestym (January 2013–July 2020), or Neupogen (July 2020–June 2023) for donor PBSC mobilization. Bivariate analysis was conducted using SPSS version 28. Statistical significance was determined at a p ‐value <.05. Results Our study included 541 allo‐HSCT donors who received Neupogen ( n = 345, 64%) or Nivestym ( n = 196, 36%) for PBSC mobilization. The median age was 47 years (range 17–76). The median donor weight was 86 kg (95% confidence interval CI: 87–91). Donors receiving Neupogen had similar pre‐G‐CSF white blood cell count, CD34 + percentages, and circulating CD34 + count compared with donors receiving Nivestym. The Neupogen group had similar median PBSC product total neutrophil count, CD34 + percentage, absolute CD34 + count, and infused CD34 + dose compared with the Nivestym group. For donors aged 35 years or younger, the median CD34 + dose was higher in donors who received Neupogen compared with Nivestym (6.9 vs. 6.3 million cells/kg, p = .044). Conclusions Nivestym demonstrated similar efficacy for PBSC mobilization compared with Neupogen among allo‐HSCT donors. In donors aged 35 years or younger, a slightly lower PBSC product CD34 + count was noted with Nivestym compared with Neupogen.
Treatment of advanced stage non-small cell lung cancer (NSCLC) has changed dramatically due to immunotherapy. However, patients without Programmed Death-Ligand 1 (PD-L1) protein expression often ...benefit less from immunotherapy. This trial is designed to test if stereotactic body radiation therapy (SBRT) to a single tumor site can significantly enhance the outcome of patients with advanced stage PD-L1(-) NSCLC when added to systemic therapy including immunotherapy.
Alliance A082002 is based on subgroup analysis from the randomized phase II PEMBRO-RT trial., PEMBRO-RT compared pembrolizumab alone or with SBRT and revealed improved progression-free and overall survival (PFS and OS, respectively) in PD-L1(-) patients when adding SBRT (8 Gy x 3 fractions). In A082002, patients without PD-L1 expression will be randomized to SBRT (8 Gy x3) plus systemic therapy vs. systemic therapy alone. The primary endpoint of the phase II portion of the trial is PFS and will require 100 patients. The primary endpoint of the phase III portion of the trial is OS and will require an additional 284 patients. This trial will clarify whether adding SBRT to systemic therapy can improve PFS and OS in a larger multi-institutional cohort. Several systemic treatment options are allowed including either immunotherapy alone or chemo-immunotherapy.
This phase II/III Alliance trial A082002 will test whether the addition of SBRT to a single tumor site will enhance the anti-tumor activity of systemic immunotherapy or chemo-immunotherapy in patients with stage IV PD-L1(-) NSCLC. It is now open in the National Clinical Trials Network (NCTN).
Olfactory Neuroblastoma is a rare malignant tumor of the olfactory tract. Reports in the literature comparing treatment modalities for this tumor are limited.
The SEER database (1973-2006) was ...queried by diagnosis code to identify patients with Olfactory Neuroblastoma. Kaplan-Meier was used to estimate survival distributions based on treatment modality. Differences in survival distributions were determined by the log-rank test. A Cox multiple regression analysis was then performed using treatment, race, SEER historic stage, sex, age at diagnosis, year at diagnosis and SEER geographic registry.
A total of 511 Olfactory Neuroblastoma cases were reported. Five year overall survival, stratified by treatment modality was: 73% for surgery with radiotherapy, 68% for surgery only, 35% for radiotherapy only, and 26% for neither surgery nor radiotherapy. There was a significant difference in overall survival between the four treatment groups (p < 0.01). At ten years, overall survival stratified by treatment modality and stage, there was no significant improvement in survival with the addition of radiation to surgery.
Best survival results were obtained for surgery with radiotherapy.
Xerostomia (severe dry mouth) is a debilitating and often permanent side effect experienced by head and neck cancer patients due to radiation injury to salivary glands. In this study, we evaluated ...the potential of ultrasound (US)-guided photoacoustic imaging (PAI) to non-invasively assess early changes in salivary gland hemodynamics following radiation therapy (RT). US-guided PAI was performed in New Zealand white rabbits to visualize and quantify the hemoglobin concentration (HbT) and oxygen saturation (%sO2) of parotid glands before and after RT. The imaging findings were validated with histology and sialometry. An early increase in parotid gland HbT and %sO2 was seen following RT. Consistent with the PAI observations, histology of salivary glands revealed dilated blood vessels, along with hemorrhaging and fibrosis. Sialometric analysis confirmed a significant reduction in stimulated saliva secretion in irradiated rabbits compared to controls. Collectively, our findings demonstrate the translational utility of US-guided PAI as a valuable tool for label-free functional imaging of salivary gland hemodynamics in vivo.
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