scholarly journals Cisplatin-based Concurrent Chemoradiotherapy Improved the Survival of Locoregionally Advanced Nasopharyngeal Carcinoma After Induction Chemotherapy by Reducing Early Treatment Failure

2021 ◽  
Author(s):  
Xing-Li Yang ◽  
Lu-Lu Zhang ◽  
Jia Kou ◽  
Guan-Qun Zhou ◽  
Chen-Fei Wu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Treatment Failure ◽  
Time Course ◽  
Concurrent Chemotherapy ◽  
P Value ◽  
Treatment Groups ◽  
Locoregional Failure ◽  
Distant Failure ◽  
Time Specific

Abstract PurposeLimited data are available on the time course of treatment failures and the nature and duration of concurrent cisplatin benefit in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC).MethodsIn total, 3123 patients with stage III-IVa NPC receiving IC followed by concurrent cisplatin or not were analysed. The cut-off value of treatment failure was calculated using the minimum P-value approach. Random survival forest (RSF) model was to simulate the cumulative probabilities of treatment failure (locoregional recurrence and /or distant metastasis) over-time, as well as the monthly time-specific, event-occurring probabilities, for patients at different treatment groups. ResultsBased on subsequent prognosis, early locoregional failure (ELRF) should be defined as recurrence within 14 months (P = 1.47×10-3), and early distant failure (EDF) should be defined as recurrence within 20 months (P = 1.95×10-4). A cumulative cisplatin dose (CCD) > 200 mg/m2 independently reduced the risk of EDF (hazard ratio (HR), 0.351; 95% confidence interval (CI), 0.169-0.732; P = 0.005). Better failure-free survival (FFS) and overall survival (OS) were observed in concurrent chemotherapy settings ([0 mg/m2 vs. 1-200 mg/m2 vs. >200 mg/m2]: FFS: 70.4% vs. 74.4% vs. 82.6%, all P < 0.03; OS: 79.5% vs. 83.8% vs. 90.8%, all P < 0.01). In the monthly analysis, treatment failure mainly occurred during the first 4 years, and the risk of distant failure in patients treated with concurrent chemotherapy never exceeded that of patients without concurrent chemotherapy.ConclusionLocoregional failure that developed within 14 months and/or distant failure within 20 months had poorer subsequent survival. Concurrent chemotherapy provides a significant FFS benefit, primarily by reducing EDF, translating into a long-term OS benefit.

Allele Level HLA Matching On Outcomes After Double Umbilical Cord Blood (dUCB) Transplantation for Hematological Malignancies: Stronger Graft Vs. Leukemia with HLA Mismatch

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1976-1976
Author(s):  
Claudio G Brunstein ◽  
Todd E. Defor ◽  
Harriet Noreen ◽  
David Maurer ◽  
Margaret L. MacMillan ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Treatment Failure ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Hla Typing ◽  
P Value ◽  
Hla Matching ◽  
Transplant Outcomes

Abstract Abstract 1976 Multiple single center and registry reports have documented the critical impact of donor-recipient HLA match on engraftment, transplant-related mortality (TRM) and survival after umbilical cord blood (UCB) transplantation. However, nearly all reports have only considered HLA A and B at antigen level and HLA DRB1 at allele level typing without consideration of HLA C or DQ. Therefore, we retrospectively performed allele level HLA typing for HLA-A, B, C, DRB1, DQB1 for UCB donor-recipient pairs in order to assess the importance of high resolution HLA typing on transplant outcomes. After 2002, most patients received a dUCB transplant in order to achieve the desired cell doses of ≥3, ≥4 and ≥5 × 10e7 NC/kg for grafts that were HLA 6/6, 5/6 and 4/6 matched by original typing resolution, respectively. Therefore, the analysis was limited to 275 recipients of dUCBT for hematological malignancy and whom DNA from both units was available. The effect of HLA match was based on the HLA type of the predominant long term engrafting unit. The median recipient age and weight was 44 years (range, 0.6–69) and 76.9 kg (range, 7.1–148), respectively. Conditioning was myeloablative (40%) consisting of cyclophosphamide (CY) 120 mg/kg, fludarabine (FLU) 75 mg/m2 and total body irradiation (TBI) 1320 cGy, or non-myeloablative (60%) consisting of CY 50 mg/kg, FLU 200 mg/m2, TBI 200 cGy with 95% receiving cyclosporine A (CsA) and mycophenolate mofetil (MMF) immunosuppression. Patients had acute leukemia (62%), standard risk disease (62%), cytomegalovirus seropositive (59%), and received at least one UCB unit that was sex mismatched to the recipient (78%). Results reported are based on the long-term predominant UCB unit. Notably, survival was not adversely affected by HLA mismatch. The probability of survival at 5 years was 46% (95%CI, 33–58%), 47% (95%CI, 38–54%) and 29% (95%CI, 13–47%) in patients engrafting with a 3–5/10, 6–8/10 and 9–10/10 HLA-matched UCB grafts, respectively (p=.47). In multivariable analysis after adjusting for disease risk, CMV serostatus, and KPS, there was similar risk of overall mortality for all groups regardless of HLA matching level. All other transplant outcomes including the incidence of acute and chronic GVHD were similar for all HLA-matching groups (data not shown). In the subset with acute leukemia (n=174), however, greater HLA mismatch was associated with a significantly lower risk of relapse without a deleterious effect on risk of TRM, resulting in a benefit in LFS (inverse of treatment failure) as shown below. Transplant Outcome for Acute Leukemia HLA 3–5/10 match (n=84) RR (95%CI), p-value HLA 6–8/10 match (n=168) RR (95%CI), p-value HLA 9–10/10 match (n=34) RR (95%CI), p-value TRM at 2 years 1.0 1.1 (0.6–2.4)
 P=.73 1.1 (0.6–2.4)
 P=.73 Leukemia Relapse 1.0 1.9 (0.9–4.3)
 P=.11 3.5 (1.3–9.5)
 P=.01 Treatment failure 1.0 1.4 (0.8–2.4)
 P=.19 2.2 (1.1–4.2)
 P=.02 Together these data indicate that UCB units with greater HLA mismatch may confer greater GVL effect without greater TRM compared to HLA better-matched UCB grafts. These results suggest importance of evaluating allele level HLA typing in the setting of dUCB transplantation. If confirmed, these results could have major implications not only on graft selection (ie avoidance of HLA matched units), but also the target size of the international UCB banking inventory. Disclosures: No relevant conflicts of interest to declare.

Outcomes of definitive chemoradiation for squamous cell carcinoma of the anus and the effect of radiation technique on hematologic parameters.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 580-580
Author(s):  
C. J. Novak ◽  
D. W. Golden ◽  
S. L. Liauw
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Intensity Modulated Radiation Therapy ◽  
Concurrent Chemotherapy ◽  
Limiting Factor ◽  
Hematologic Toxicity ◽  
Bone Marrow Toxicity ◽  
Locoregional Failure ◽  
Distant Failure

580 Background: Chemotherapy-radiation (CRT) is an established therapy for squamous cell carcinoma of the anus. A limiting factor in the successful completion of CRT is bone marrow toxicity. The effect of intensity modulated radiation therapy (IMRT) on marrow toxicity is not well defined. We evaluated the effect of IMRT on the severity of cytopenias for patients receiving CRT. We also explored the influence of cytopenias on disease outcome both pre-CRT or during CRT. Methods: 43 patients were treated with CRT between 1994-2010. The median delivered dose was 50.4 Gy (range, 32.4-59.4). 31 patients (72%) were treated with IMRT. All patients received concurrent chemotherapy, usually 5FU and mitomycin-C (n = 34, 79%). White blood cell (WBC), hemoglobin (Hg), and platelet counts were recorded pre- CRT, weekly during CRT, and within 7 days post-CRT. Hematologic values were analyzed according to type of RT and for association with treatment outcome. Results: 2-year locoregional failure (LRF) and distant failure were 14% and 14%, respectively. 21 patients required a treatment break due to any cause. In 9 (43%) patients the break was due to hematologic toxicity. 34 patients had complete blood values available. IMRT did not affect the rate of ≥ grade 2 cytopenia (p = 0.64) or median treatment nadirs; Hg (9.1 vs. 8.3 g/dL, p = 0.24), WBC (1.7 vs. 1.2 K/uL, p = 0.95), or platelets (90.5 vs. 61.5 k/uL, p = 0.88). Median time to nadir was not different for WBC (7 vs. 7 days, p = 0.36) or Hg (36 vs. 22 days, p = 0.29), but patients treated with IMRT did have a delayed platelet nadir (33 vs. 14 days, p = 0.01). Hg nadir ≤ 9 g/dL was associated with a higher rate of 2- year LRF (> 9 g/dL 100% vs. ≤ 9 g/dL 73%, p = 0.03). No other hematologic values were associated with LRF. Conclusions: In this cohort of patients, nearly 50% of patients required a treatment break, which was related to a cytopenia 43% of the time. IMRT did not appear to have significant impact on acute marrow toxicity, although sample size may limit our power to detect a difference. Low Hg during CRT appears to influence LRF. More detailed dose volume histogram analysis will be useful to further explore how IMRT might influence acute hematologic toxicity, and therefore treatment outcomes. No significant financial relationships to disclose.

scholarly journals Effects of catheter ablation on left atrial performance in different types of atrial fibrillation: a strain study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Katbeh ◽  
T De Potter ◽  
P Geelen ◽  
E Stefanidis ◽  
K Iliodromitis ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Time Course ◽  
Public Institution ◽  
P Value ◽  
Funding Source ◽  
Functional Changes ◽  
Af Recurrence

Abstract Background Atrial structural and functional changes may develop as a result of catheter ablation (CA) in patients with paroxysmal and persistent atrial fibrillation (AF). However, the relation between AF recurrence and atrial performance following CA is still under debate. Our aim is to describe the long-term effects of CA on LA remodeling and its correlates to the maintenance of sinus rhythm (SR). Methods We prospectively enrolled 178 consecutive patients (age: 63±9 years, 35% females) with paroxysmal AF undergoing first-CA (67%) or redo-CA (22%), and 20 individuals (11%) with long-standing persistent AF (PAF) undergoing first CA. All patients underwent comprehensive transthoracic echocardiography at baseline and at 12-month follow-up, including the assessment of reservoir and contractile strain (LAS) using two dimensional speckle tracking echocardiography in all three apical views. The study population was divided in two sub-groups according to AF recurrence during follow-up. Results During one-year follow-up, 144 (81%) patients maintained SR whereas 34 (19%) patients had AF recurrence [first-CA group 16 (13%), redo-CA group 8 (20%) and PAF group 10 (50%)]. Improvement of LAS was observed only in patients with paroxysmal and long-standing persistent AF who underwent the first CA and who remained in SR (Figure 1A, 1C). In contrast, recurrent AF was associated with absence of LAS improvement (Figure 1A, 1C). Different time course of LA performance was observed in the redo-CA group, i.e. LAS remained unchanged from baseline regardless of long-term maintenance of SR (Figure 1B). Moreover, at follow-up, no significant differences in LAS between redo-CA patients with SR versus AF were observed. Of note, in patients with long-standing persistent AF and SR, follow-up LAS increased to values observed in the redo-CA group. Conclusion LA performance following CA is strongly affected by complex interplay between extent of atrial electro-structural remodeling and CA procedure. Repeated wide CA might affects negatively LA compliance and contractility despite SR restoration. Figure 1. Reservoir and contractile LAS at Baseline and 12-month follow-up in the First-CA (1A), the Redo-CA (1B) and the long-standing persistent AF (1C) groups in patients who maintained SR versus patients who had AF recurrence. *p value &lt;0.05 (baseline vs. follow-up). Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh).

scholarly journals The Relationships Between Radiation Dosage and Long-term Swallowing Kinematics and Timing in Nasopharyngeal Carcinoma Survivors

Dysphagia ◽  
2021 ◽  
Author(s):  
Dai Pu ◽  
Victor H. F. Lee ◽  
Karen M. K. Chan ◽  
Margaret T. Y. Yuen ◽  
Harry Quon ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Radiation Dosage ◽  
Intensity Modulated Radiation Therapy ◽  
Concurrent Chemotherapy ◽  
Swallowing Function ◽  
Pharyngeal Constriction ◽  
The Relationship ◽  
Higher Doses ◽  
Inferior Pharyngeal Constrictor

AbstractThis study aimed to investigate the relationship between intensity-modulated radiation therapy (IMRT) dosimetry and swallowing kinematic and timing measures. Thirteen kinematic and timing measures of swallowing from videofluoroscopic analysis were used as outcome measures to reflect swallowing function. IMRT dosimetry was accessed for thirteen swallowing-related structures. A cohort of 44 nasopharyngeal carcinoma (NPC) survivors at least 3 years post-IMRT were recruited. The cohort had a mean age of 53.2 ± 11.9 years, 77.3% of whom were male. There was an average of 68.24 ± 14.15 months since end of IMRT; 41 (93.2%) had undergone concurrent chemotherapy. For displacement measures, female sex and higher doses to the cricopharyngeus, glottic larynx, and base of tongue were associated with reduced hyolaryngeal excursion and pharyngeal constriction, and more residue. For timing measures, higher dose to the genioglossus was associated with reduced processing time at all stages of the swallow. The inferior pharyngeal constrictor emerged with a distinctly different pattern of association with mean radiation dosage compared to other structures. Greater changes to swallowing kinematics and timing were observed for pudding thick consistency than thin liquid. Increasing radiation dosage to swallowing-related structures is associated with reduced swallowing kinematics. However, not all structures are affected the same way, therefore organ sparing during treatment planning for IMRT needs to consider function rather than focusing on select muscles. Dose-response relationships should be investigated with a comprehensive set of swallowing structures to capture the holistic process of swallowing.

Concurrent and Adjuvant Chemotherapy for Nasopharyngeal Carcinoma: A Factorial Study

2004 ◽  
Vol 22 (13) ◽  
pp. 2643-2653 ◽  
Author(s):  
Dora L.W. Kwong ◽  
Jonathan S.T. Sham ◽  
Gordon K.H. Au ◽  
Daniel T.T. Chua ◽  
Philip W.K. Kwong ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Nasopharyngeal Carcinoma ◽  
Cox Model ◽  
Statistical Significance ◽  
Distant Metastases ◽  
Neck Node ◽  
Free Survival ◽  
Treatment Groups ◽  
Locoregional Failure ◽  
Favorable Prognostic Factor

Purpose To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC). Patients and Methods Patients with Ho's stage T3 or N2/N3 NPC or neck node ≥ 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B. Results Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P = .14 and .06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P = .026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P = .39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P = .83 and .69; n = 111 v 108). DMR and LRFR were not reduced with AC (P = .34 and .15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P = .009). Conclusion An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.

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