Stage IIIB Patients Research Articles

Association of HPV Genotyping with HIF1-Alpha in Advanced Cervical Cancer on Response to Radiotherapy

AIM: This study aims to determine the relationship between the HPV genotype in uterine cervical cancer and the expression of HIF-1α due to tissue hypoxia and its impact on radiation response. METHODS: This study is an analytic and observational study with a cross-sectional design with the inclusion criteria in this study that was new cervical cancer Stage IIB, IIIA, IIIB, and IVA patients treated at the oncology polyclinic who had never undergone radiotherapy and would be treated with radiation. RESULTS: Sixty patients advanced cervical cancer aged 25 to >45 years were involved patients. The majority had HPV genotype 16 infections. There was no significant relationship between treatment response and HPV genotype (HPV 16 genotype [p = 0.844], HPV 18 genotype [p = 0.161], other HPV genotypes [p = 0.108]), radiation response with HIF-1α expression (p = 0.503; OR 1.569 [0.417–5.899]), HIF1α expression with HPV genotype (HPV genotype 16 (p = 0.648; OR 1,357 [0.356–5.041]), HPV 18 genotype (p = 0.344; OR 1,458 [0.089–2.373]), and other HPV genotypes (p = 0.505; OR 1.667 [0.368–7.553]) as well as HIF-1α expression and HPV genotypes to radiation response (p > 0.05). CONCLUSION: Cervical cancer with infection with HPV Genotype 18 tends to express HIF1α strongly and increased partial radiation response. Overall statistically, there was no significant association between infection with certain genotypes of HPV with radiation response or HIF-1α expression in tumor tissue with radiation response.

Treatment patterns and long-term survival outcomes for patients with stage III non-small cell lung cancer: A retrospective study.

Lung cancer is the leading cause of cancer-related deaths in Australia with poor long-term survival outcomes. Stage III non-small cell lung cancer (NSCLC) is a highly heterogenous group with diverse tumor characteristics and multiple, possible treatment options. We present retrospective data on patient characteristics, treatment patterns, and long-term outcomes in stage III NSCLC patients treated at a single cancer center in New South Wales, Australia. Stage III NSCLC patients were identified from the 'Nepean Cancer Research Biobank'. Patient demographics, cancer-related information, and long-term follow-up data were collected and analyzed. A total of 88 patients were eligible for analysis with 61% of them diagnosed as stage IIIA, 35% IIIB, and 4% IIIC. Induction chemotherapy was administered in 20% of the patients. Overall, 48% of the study population underwent surgery, and 38% underwent concurrent chemoradiotherapy (CCRT). Both median progression-free survival and overall survival (OS) were superior in stage IIIA patients in comparison to stage IIIB (and IIIC) patients (22 vs. 11 months, p=.018; and 58 vs. 19 months, p=.048, respectively). Patients who were younger (<65 years old), good Eastern Cooperative Oncology Group performance status (ECOG PS <2), and females had better prognosis on univariate analysis. There was a nonstatistically significant trend toward better median OS with CCRT in comparison to surgery (58 vs. 37 months, p=.87). Long-term outcomes remain poor, and hence better treatment strategies are urgently needed in stage III NSCLC. Equally, more robust, prospective studies would help delineate the optimal treatment modality in these patients.

The efficacy of neoadjuvant EGFR-TKI therapy combined with radical surgery for stage IIIB lung adenocarcinoma harboring EGFR mutations: A retrospective analysis based on single center.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) could provide survival benefits for locally advanced EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC). However, the role of radical surgery for EGFR-TKI treated stage IIIB EGFRm NSCLC remains controversial. This study attempted to assess the feasibility of neoadjuvant EGFR-TKI followed by radical surgery for stage IIIB EGFRm NSCLC. Between 2013 and 2020, EGFRm lung adenocarcinoma (LUAD) patients in clinical stage IIIB undergoing neoadjuvant EGFR-TKI followed by surgery (T-S-Arm) and EGFR-TKI alone (T-Arm) were reviewed retrospectively in Shanghai Pulmonary Hospital (SPH). The chi-square test, Student's t-test or Fisher's exact test was performed for analysis of baseline characteristics. Progression-free survival (PFS) was estimated using the Kaplan-Meier analysis. Multivariate Cox regression analysis was used to identify independent predictors of progression. A total of 43 patients were divided into T-S-Arm (n = 21) and T-Arm (n = 22). Patients were well-balanced between the two arms. The majority of patients were female (n = 25, 58.1%), non-smokers (n = 35, 81.4%), first-generation of EGFR-TKI treatment (n = 39, 90.7%), and exon 19 deletions (19-DEL) (n = 26, 60.5%). The median diagnostic age was 63.0 years [interquartile range (IQR), 54.0-67.5 years). At the cut-off date with June 30th 2022, median follow-up time was 28 months (IQR, 20-39 months). Neoadjuvant EGFR-TKI treatment followed by radical surgery could significantly improve the median PFS compared with patients underwent EGFR-TKI alone (23.0 months vs 14.5 months, P = 0.002). Multivariate Cox regression analysis demonstrated that radical surgery (T-S-Arm vs. T-Arm, HR: 0.406; 95% CI: 0.207-0.793, P = 0.027) was the only independent predictor for disease progression. The stratified analysis demonstrated patients with N2 disease could benefit from radical surgery (HR, 0.258; 95% CI, 0.107-0.618), especially for patients harboring L858R mutation (HR, 0.188; 95% CI, 0.059-0.604). For stage IIIB EGFRm NSCLC patients, the prognosis might be improved by neoadjuvant EGFR-TKI followed by radical surgery versus EGFR-TKI alone, especially for those with N2 disease and harboring L858R mutation.

The management of light chain (AL) amyloidosis in Europe: clinical characteristics, treatment patterns, and efficacy outcomes between 2004 and 2018

Systemic light-chain (AL) amyloidosis is a rare and debilitating disease. Advances have been made in new treatments in recent years, yet real-world data on the management of the disease are scarce. EMN23 is a retrospective, observational study of patients who initiated first-line treatment in 2004–2018 in Europe, presenting the demographics, clinical characteristics, treatment patterns, and outcomes, from 4480 patients. Regimens based on bortezomib were the most frequently used as first-line therapy; only 6.2% of the patients received autologous stem cell transplant. Hematologic responses improved post-2010 (67.1% vs 55.6% pre-2010). The median overall survival (OS) was 48.8 (45.2–51.7) months; 51.4 (47.3–57.7) months pre-2010 and 46.7 (41.3–52.2) months post-2010. Early mortality was 13.4% and did not improve (11.4% vs 14.4% pre- and post-2010); furthermore, it remained high in patients with advanced cardiac disease (over 39% for stage IIIb). There was a significant improvement for stage IIIa (14.2 vs 30.7 months, p = 0.0170) but no improvement for stage IIIb patients (5.0 vs 4.5 months). This European real-world study of AL-amyloidosis emphasizes the unmet needs of early diagnosis, and the lack of improvement in survival outcomes of the frail stage IIIb population, despite the introduction of new therapies in recent years.

Long-term outcomes of stage IIB–IV melanoma patients: nationwide data from Norway

Aim: This study was performed to investigate the characteristics and overall survival (OS) of patients with completely resected stage IIB-IV cutaneous melanoma identified in the Cancer Registry of Norway. Methods: A retrospective cohort study of all adult patients with stage ≥IIB cutaneous melanoma was performedin Norway (January 2008 to December 2018), excluding patients with stage IV melanoma without evidence of surgery. Results: 5-year OS varied by stage (IIB 65%, IIC 38%, IIIA 79%, IIIB 66%, IIIC 52%, IIID 37%and IV 39%). Adjusted Cox models showed that stage IIIA and IIIB patients showed similar survival to stage IIB patients (hazard ratio [95% CI]: IIIA 0.67 [0.44-1.04]; IIIB 1.18 [0.96-1.45]), while all other stages had lower survival than IIB. Conclusion: Survival for stage II patients, particularly IIC, can be poor and in some cases worse than patients with more advanced stage melanoma. Our data highlight an unmet need for effective adjuvant treatment options amongstage IIB/C patients.

Association of lymph node metastases, grade and extent of mesenteric lymph node dissection in locoregional small intestinal neuroendocrine tumors with recurrence-free survival.

We aimed to assess the prognostic impact of tumor- and patient-related parameters in patients with stage I-III small intestinal neuroendocrine tumors (SI-NETs), who underwent locoregional resective surgery (LRS) with curative intent. We included 229 patients with stage I-III SI-NETs diagnosed from June 15, 1993, through March 8, 2021, identified using the SI-NET databases from five European referral centers. Mean ± SD age at baseline was 62.5 ± 13.6 years; 111/229 patients were women (49.3%). All tumors were well-differentiated; 160 were grade 1 (G1) tumors, 51 were G2, two were G3 and 18 tumors were of unspecified grade (median Ki-67: 2%, range 1%-50%). One-hundred and sixty-three patients (71.2%) had lymph node (LN) involvement. The median number of retrieved lymph nodes was 10 (0-63), whereas the median number of positive LNs was 2 (0-43). After a mean ± SD follow-up of 54.1 ± 64.1months, 60 patients experienced disease recurrence at a median (range) of 36.2 (2.5-285.1) months. The 5- and 10-year recurrence-free survival (RFS) rates were 66.6% and 49.3% respectively. In univariable analysis, there was no difference in RFS and overall survival (OS) between LN-positive and LN-negative patients (log-rank, p=.380 and .198, respectively). However, in stage IIIb patients who underwent mesenteric lymph node dissection (MLND) with a minimum of five retrieved LN (n=125), five or more LN metastases were associated with shorter RFS (median RFS [95% CI]=107.4 [0-229.6] vs. 73.7 [35.3-112.1]months; log-rank, p=.048). In addition, patients with G2 tumors exhibited shorter RFS compared to patients with G1 tumors (median RFS [95% confidence interval (CI)]=46.9 [36.4-57.3] vs. 120.7 [82.7-158.8]months; log-rank, p=.001). In multivariable Cox-regression RFS analysis in stage IIIb patients, the Ki-67 proliferation index (hazard ratio=1.08, 95% CI=1.035-1.131; p < .0001) and the number of LN metastases (hazard ratio=1.06, 95% CI=1.001-1.125; p=.047) were independent prognostic factors for RFS. In conclusion, LRS with a meticulous MLND and a minimum number of five harvested LNs appears to be critical in the surgical management of SI-NET patients with locoregional disease. In patients who underwent LRS and MLND, the Ki-67 proliferation index and the LN metastases count were independent predictors of RFS.

The Survival and Prognosis Characteristics of Primary Esophageal Small-Cell Carcinoma.

Objective To comprehensively explore the survival characteristics of primary esophageal small-cell carcinoma (PSCCE) and identify the main factors affecting the prognosis. Methods The clinical and follow-up data of PSCCE patients admitted to the Fourth Hospital of Hebei Medical University from 2006 to 2010 were retrospectively analyzed. The primary endpoint was five-year survival. Survival curves were drawn using the Kaplan-Meier method, and log-rank test was used to compare the differences in survival rates among the groups. Cox regression models were used to analyze prognostic factors. Results A total of 119 eligible patients were retrieved. Median survival was 27 months (3-100 months). Changes in overall survival (OS) in PSCCE patients were associated with TNM stage (P = 0.007), T stage (P = 0.049), and lymph node metastasis (P = 0.004). When TNM was in stage I-IIb, lymph node metastasis (P = 0.003) or combined adjuvant therapy (P = 0.004) was an independent factor affecting OS. Survival analysis showed that TNM staging had no predictive value for 5-year survival time or disease-free survival (DFS) of PSCCE (P > 0.05). Conclusion TNM stage, T stage, and lymph node metastasis were related to the survival of patients. Negative lymph node metastasis and treatment are independent prognostic factors in PSCCE TNM stage I-IIb patients.

What are the problems with the current staging of discontinuous tumour nodules (DTNs) in colorectal carcinoma? Is there a better way?

Discontinuous extramural tumour nodules (DTNs) are deposits of metastatic carcinoma in soft tissue not associated with lymph nodes. Although they are established as an adverse prognostic factor in colorectal carcinoma (CRC), under the AJCC eighth edition staging system their presence does not upstage patients who also have lymph node metastases. Counterintuitively, in some situations the presence of lymph node metastases may in effect downstage a patient with DTNs from pN1c to pN1a/b. Therefore, we sought to critically assess the significance of DTNs in a large unselected single institution cohort of patients undergoing surgical resection for CRC. Of 3822 CRC patients undergoing surgical resection from 2005 to 2021, DTNs were present in 686 (18.0%). In univariate (HR=2.687, 95CI 2.355-3.065; p<0.001) and multivariate analysis (HR=1.805, 95CI 1.529-2.132; p<0.001) in a model including age, gender, stage, grade, location, lymph node ratio and apical lymph node status, DTNs were associated with worse overall survival (OS). N1c patients (DTN present but no nodal metastasis) demonstrated worse OS compared to the current pN1a group (p<0.001) and were least different to the current pN2a group (p=0.571). Within the current N1a (p=0.013), N1b (p=0.004) and N2a (p=0.002) groups, patients who also had DTNs had worse OS. DTNs were associated with worse OS for all stage III CRCs combined (p<0.001), and for stage IIIB (p<0.001) and stage IIIC (p=0.007) individually. We conclude that DTNs are an independent adverse prognostic factor that should be considered in the staging system in a way that is additional to (rather than integrated with) the number of involved lymph nodes. We then assess a simple suggestion for how this could be achieved by increasing the overall stage by one group in the presence of DTNs (requiring the creation of a new stage IIID).

Outcomes of intermediate stage varus ankle arthritis treated by supramalleolar osteotomy.

To evaluate the outcomes of intermediate stage varus ankle arthritis treated by supramalleolar osteotomy. Clinical data of 57 patients with varus arthritis who underwent supramalleolar osteotomy at our hospital between March 2018 and December 2019 were retrospectively analyzed. The patients were grouped according to the Takakura classification, and assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score and the Visual Analogue Score (VAS). Tibial anterior surface (TAS) angle and talar tilt (TT) angle were measured at the weight-bearing anteroposterior view. Tibial lateral surface (TLS) angle was measured at the weight-bearing lateral view. The differences in the above indicators of patients with different stages of varus ankle arthritis before and after treatment were analyzed. The patients were followed up for an average of 31.9 ± 5.8months. Upon the last follow-up, the AOFAS score was 84.1 ± 9.7, the VAS score 2.2 ± 1.3, the TAS angle 92.4 ± 5.5°, the TLS angle 79.3 ± 5.3°, and the TT angle 3.7±3.4°, which were significantly different from the preoperative levels (64.2 ± 14.6, 4.5 ± 1.8, 80.5 ± 6.7°, 74.9 ± 4.6°, and 5.2 ± 64.1°, respectively) (p < .05). There were significant differences in AOFAS and VAS scores before surgery and upon the last follow-up in each group (p < .05). The postoperative TT angle was significantly different from the preoperative level in stage IIIb patients (p = .003). Supramalleolar osteotomy achieved good short-to mid-term clinical outcomes for intermediate stage varus ankle arthritis. This procedure could significantly improve the TAS and TLS angles of the patients at any stage and the TT angle of stage IIIb patients.

The Correlation of Fibronectin and Vimentin Expression on Anthracycline-Based Neoadjuvant Chemotherapy Response in Stage IIIA and Luminal Subtype IIIB Breast Cancer

ABSTRACT Introduction: Breast cancer has a phenotype of interconnected epithelial cells and then changes to mesenchymal cells through activation of epithelial-to-mesenchymal transition (EMT). Vimentin, as the main component of forming a cell frame, can be used as a marker of the EMT process. Fibronectin is an extracellular glycoprotein that binds to receptor proteins known as EMT markers. This study aims to evaluate the correlation between these proteins on neoadjuvant chemotherapy (NAC) response. Methods: This study was carried out from November 2029 to March 2020 and used the consecutive sampling of Stage IIIA and Luminal Subtype IIIB breast cancer patients after chemotherapy using anthracycline. Subject obtained from outpatient at oncological surgery of Dr. Saiful Anwar Hospital Malang, Indonesia. Fibronectin and vimentin expression was measured from paraffin block by immunohistology staining. Statistical analysis used correlation tests and logistic regression with a significant level of P &lt; 0.05. Results: Mean patient age in this study was 54 ± 4.5 years old, and most of the patients were Stage IIIB patients (98.48%). Most patients have negative vimentin and fibronectin expression. In this study, we found a significant relationship between vimentin expression and NAC response with P = 0.000 and a correlation coefficient was 0.440. Conclusion: There was a significant correlation between vimentin expression and the response of NAC. There is a significant correlation between fibronectin expression and the response of NAC. Fibronectin expression can be used as a predictive factor for nac in stage iiia breast cancer patients.

P1714: HEALTHCARE RESOURCE UTILIZATION IN PATIENTS WITH LIGHT CHAIN AMYLOIDOSIS IN EUROPE

Background: Systemic light chain (AL) amyloidosis is a rare plasma cell disease characterized by the accumulation of amyloid fibrils in various tissues and organs throughout the body, leading to multiorgan dysfunction. Beyond anti-clonal therapy, this disease treatment requires multidisciplinary teams and resources to manage its multiorgan complications, however, the burden of the disease for health care system and health care resource use (HCRU) remain underexplored. Aims: To assess the HCRU in patients (pts) with AL amyloidosis across several European countries. Methods: EMN23, a retrospective, multicenter study, investigated the demographic and clinical characteristics, the treatment pathways, and the HCRU of adult pts with AL amyloidosis who initiated treatment in 2004–2018 from 13 sites across 10 European countries. The HCRU analysis on the 2011-2018 period included patient data from 7 countries (Greece, France, the Netherlands, Portugal, the Czech Republic, Austria, and Spain [only dialysis information available]). Patients who participated in clinical trials at any line were excluded. HCRU measures included hospitalizations, imaging examinations, adverse events of special interest (AESIs; Intensive Care Unit admission, Heart Failure, Need for pacemaker, Infections requiring hospitalization, Peripheral neuropathy), and dialysis information. Results: In 2011-2018, HCRU data and safety information were available for 462 pts (531 pts. with dialysis data). Most (63.4%) pts were males ≥65 years old (52.4%). At baseline, 41.6% (192/462) pts had 1 organ involved, 36.1% (167/462), had 2 and 20.8% (96/462) pts had ≥3 organs involved. The proportions of pts per the Eastern Cooperative Oncology Group (ECOG) status of 0, 1, 2, and 3 were 20.8% (96/462), 24.9% (115/462), 19.0% (88/462), and 7.8% (36/472), respectively; (not reported for 26.4% (122/462) pts). At diagnosis, Mayo 2004/European cardiac stages I, II, IIIa, and IIIb distribution was 75 (16.2%), 126 (27.3%), 127 (27.5%), and 59 (12.8%), respectively (Table 1) and was unknown for 75 (16.2%) pts. In 2011-2018, the number of pts with ≥1 hospitalization was 280 (60.6%). Duration of hospitalization is longer for patients stage IIIa and IIIb compared to lower cardiac stages (Table). Ultrasound and X-rays were the most common imaging exams across most cardiac stages (Stage I: 45.3%; Stage II: 42.1%, Stage IIIa: 47.2%; Stage IIIb: 39.0%), but MRIs and scintigraphy were also used commonly (see Table). At first-line, the proportions of pts treated with immunomodulatory (IMiD)-based regimens, bortezomib-based regimens, chemotherapy, and autologous stem cell transplantation were 2.2% (10/462), 62.3% (288/462), 12.6% (58/426) and 11.5% (53/462), respectively. The proportions of pts with ≥1 SAE and ≥1 AESI were 49.4% (228/462) and 28.8% (133/462), respectively. Infectious complication and heart failure were common reasons for hospitalization, with, half of the AESI records for cardiac stage IIIb patients being cardiac failure and ~1/10 AESI records being ICU admissions. A median number of 70.5-139.6 dialyses per pt per year were received by 70 (13.2%) pts, across cardiac stages. Image:Summary/Conclusion: The current analysis shows that in the recent years (post-2010), the burden of HCRU for pts with AL Amyloidosis was considerable, across all Mayo2004/European cardiac stages. The main burdensome components were hospitalizations and dialysis. A cost-of-illness study from the healthcare perspective will be conducted, to reveal the cost burden on the healthcare system of pts with AL amyloidosis in Europe.

The Prognostic Significance of Hydronephrosis and Role of Ureteric Stenting in Cervical Cancer Patients Treated with Radical Radiation Therapy, Real World Outcomes from a Regional Cancer Centre, South India

Background: The incidence of renal failure in carcinoma cervix ranges from 14% to 44·2%. The interventional strategies like ureteric stenting and percutaneous nephrostomy can be considered to improve renal function. The primary objective of our study is to analyze the impact of hydroureteronephrosis [HUN] in the outcome of cervical cancer patients treated with radical radiation. The secondary objective is to analyze the role of ureteric stenting to protect the renal function while proceeding with radical radiation. Methods: In this retrospective study, all patients with stage IIIB cervical cancer treated with radical radiation therapy at our institution from January 2010 to December 2019 were included. Results: Among the total 483 stage IIIB patients, 146 patients [30·22%] had hydronephrosis.Thirty eight [26·02%] out of 146 patients with HUN underwent ureteric stenting. The five year overall survival [OS] was 61·4 ± 0·04 % and on subset analysis, overallsurvival was 65·7 ± 0·05 % for patients without HUN and 50·6 ± 0·06 % for patientswith HUN. [P value &lt;0·001]. Among patients with hydronephrosis, those with bilateral hydronephrosis or serum creatinine &gt;1·1 mg/dL have benefitted more from stenting. In this high risk subgroup, the one year overall survival was 65·2 ± 0·11 % and 42·4 ±0·13 % for patients with and without stenting. [p value 0·07]. No major stent related morbidity occurred. Conclusions: Hydronephrosis in cervical cancer patients indicates bad prognosis which results in decreased survival. The presence of hydronephrosis should be redesignated as a separate substage, IIIB2 in future FIGO updates, for better prognostication and treatment recommendations. The relief of obstructive uropathy should be sought out inpatients with serum creatinine levels &gt; 1·1 mg/dL or bilateral hydronephrosis before theinitiation of oncological treatment.

Clinical value of alveolar lavage supernatant specimens in the detection of the EGFR gene mutation in patients with non-small cell lung carcinoma.

BackgroundThis study sought to compare the consistency of the epidermal growth factor receptor (EGFR) gene mutation detection results in the supernatant of alveolar lavage specimens to the tissue sample results, and the consistency of the blood EGFR gene mutation detection results to the tissue detection results.MethodsIn total, 29 patients with non-small cell lung carcinoma (NSCLC) were selected, and their bronchoalveolar lavage fluid (BALF) was collected. The supernatant and precipitate were separated by centrifugation. Deoxyribonucleic acid (DNA) was extracted from the supernatant, and blood and tumor tissues were collected to detect patients’ EGFR gene mutation status.ResultsOf the 29 enrolled patients, 12 of the 23 tissue-biopsy patients (52.2%) were positive for EGFR mutations, 11 of the 28 blood-test patients (39.2%) were positive for EGFR mutations, and 13 of the 29 cases of the BALF-test patients (44.8%) were positive for EGFR mutations. The most common mutations were the exon 19 deletion mutation and the L858R point mutation. The EGFR gene mutation rate was higher in female, young, non-smoker, and stage IIIB patients (than stage IV patients), but the differences were not statistically significant (all P>0.05). Of the 29 NSCLC patients tested for the EGFR gene mutation, the BALF supernatant and blood results were the same for 27 patients (coincidence rate: 93.10%). Of the 23 of the 29 enrolled patients tested for the EGFR gene mutation, the BALF supernatant and tissue test results were the same for 21 patients (coincidence rate: 91.30%). Further, the blood-test and the tissue test results were the same for 20 patients (coincidence rate: 86.96%).ConclusionsThe EGFR gene mutation rate was high in NSCLC patients. The coincidence rate of the EGFR gene mutation detection results between BALF supernatant and tumor tissues was slightly higher than that of the blood and tumor tissue EGFR gene mutation detection results.

Role of prognostic scores in the evolution of renal involvement in patients with multiple myeloma after bone marrow transplantation

Introduction: Treatment of multiple myeloma (MM) with chemotherapy and autologous bone marrow transplantation (BMT) commonly results in renal dysfunction associated with early mortality. Prognostic scores for MM are assessed by either Durie and Salmon (DS) or International Staging System (ISS) methods. Few studies have examined the relationship between these scores and renal damage after BMT. Aims: To evaluate DS and ISS prognostic scores as they relate to renal function and mortality in MM patients who have undergone BMT. Methods: Retrospective, observational cohort of 95 MM patients who underwent BMT between 2012 and 2014. Renal function was assessed using data on proteinuria, serum creatinine, and estimated glomerular filtration rate from the time of hospital admission to 6 months post-BMT. Results: Neither score was significantly associated with death or proteinuria, but patients in DS stage IIIB were 12.8 times more likely to experience renal dysfunction than those in DS stage I–II. Both DS and ISS scores reflected a progressive increase in the chance of renal functional impairment with increased disease staging. Conclusions: The prognostic methods studied were useful in the initial recognition of renal dysfunction and after 6 months post BMT, the DS score was still able to predict the reduction of eGFR. Patients in the advanced stages of MM were associated with altered renal function, and these results could help to establish early treatment strategies to reduce the risk of renal damage.

Secondary and Quaternary Delays in the Diagnosis of Breast Cancer: Are the Physicians Responsible too?

Causes of delay in presentation of breast cancer has been categorised into 'Primary Delay' (delay by the patient or her family); 'Secondary Delay' (delay by the doctors in the first contact - family physician or quacks/alternative medicine practitioners); 'Tertiary Delay' (delay in the system in a specialist breast care unit e.g. waiting list, delayed reporting, doctors on leave, strikes); and 'Quaternary Delay' (e.g. patient hopping from one competent breast cancer specialist to another or mid-course attrition to alternative treatments). In India, many patients have blind belief and high attrition towards the quacks and alternative medicine practitioners. Our study was to assess whether these 'Secondary and Quaternary Delays', particularly the attrition towards the alternative non-modern medical practitioners, have any effect on the delayed presentation and advancement of the overall anatomical staging among the breast cancer patients. We performed a retrospective observational study, based on 'Triple Assessment' and pre-structured Questionnaire. All pathologically confirmed female breast cancer patients admitted from 02/2017 to 08/2018 in the department of General Surgery in our Institute were included. Male breast cancer, histopathologically unconfirmed/inconclusive breast lumps, patients with previous breast surgery/radiotherapy/chemotherapy were excluded. Data from 267 patients was analysed. The mean age at presentation of breast cancer was 47.54years. The average delay between the onset of the first symptom and the histological diagnosis was 13.76 ± SD 13.08months. About half (50.2%) of our patients visited the non-modern medical practitioners at least once during their disease. The mean delay in diagnosis was significantly higher (p < 0.0001) among them. The average 'Secondary Delay' was significantly higher among those who visited the non-modern medical practitioners (9.7 ± SD 9.38months). The average delay between the visit to the first doctor and the histological diagnosis was also significantly higher among them (18.35 ± 14months). Patients with attrition to non-modern medical practitioners also were diagnosed in higher cT stages: cT4a (66.67%, 2 of 3) and cT4b (60%, 33 of 55). Most (56.9%) of stage IIIB patients visited the non-modern medical practitioners before their diagnosis. Patients who visited the non-modern medical practitioners had significantly more delay in the diagnosis of breast cancer. The 'Secondary and Quaternary Delays' form the major portion in the overall delay and lead to advancement of the anatomical staging of the disease. Creating public awareness, proper training and 'continued medical education' for primary care physicians, and the AYUSH practitioners are required. Further population-based studies are advised.

Significance of Magnetic Resonance Imaging Combining with Detection of Serum HE4, TSGF, and CD105 Levels in Diagnosis and Treatment of Moderate to Advanced Cervical Cancer.

To explore the significance of magnetic resonance imaging (MRI) combining with detection of serum HE4, TSGF, and CD105 levels in diagnosis and treatment of moderate to advanced cervical cancer. By means of retrospective study, 50 patients diagnosed with moderate to advanced cervical cancer by cervix biopsy pathology examination in our hospital from October 2018 to October 2019 were selected as the study group, and another 50 healthy individuals who did not have cervical cancer after routine gynecological examination and conventional ultrasound examination in the same period were selected as the control group. At the time of enrollment and 3 months after treatment, all study subjects received MRI examination and serological examination, and their HE4 and TSGF levels were measured by the enzyme-linked immunosorbent assay (ELISA) and chromatography method, respectively, and additionally, the immunohistochemistry SP method was adopted for patients in the study group to measure the microvessel density (MVD) marked by CD105. The relationship between MRI staging and FIGO staging was assessed, the efficacy of combining MRI with detection of serum HE4, TSGF, and CD105 levels in diagnosing moderate to advanced cervical cancer was calculated by plotting the ROC curve, and the imaging changes and serological changes of tumor tissue before and after treatment were analyzed. There were 3 of 4 patients in stage IIa and 14 of 15 patients in stage IIIb presenting MRI findings compatible with clinical examinations; 26 patients in stage IIb and 5 patients in stage IVb presenting MRI findings totally compatible with clinical examination. Before treatment, MRI finding of cervical lesion was irregular soft tissue mass, T1WI appeared isointensity or hyperintensity, and obvious lesion enhancement could be seen by enhanced scan. T2WI appeared mixed signal intensity or hyperintensity, with necrotic tissue and fat suppression being hyperintensity. After treatment, lesions shrunk, originally abnormal signals in 5 patients disappeared, and T1WI and T2WI signals in 45 patients presented no difference compared to before treatment. After T1WI enhancement, mild enhancement could be seen in 41 cases and no enhancement in 4 cases. The CD105-MVD of the study group was (68.98 ± 5.23); before and after treatment, the differences in HE4 and TSGF levels between the study group and the control group were significant (P < 0.001). The sensitivity, specificity, and accuracy rate of diagnosis of MRI diagnosis were respectively 82.0% (41/50), 90.0% (45/50), and 86.0% (86/100), and for the diagnosis combining with serum HE4, TSGF, and CD105 levels, they were 96.0% (48/50), 96.0% (48/50), and 96.0% (96/100), respectively, and AUC (95% CI) = 0.960 (0.908-1.000). MRI staging is objective and accurate and has higher sensitivity when combined with serum HE4, TSGF, and CD105 levels in diagnosing moderate to advanced cervical cancer. All MRI, HE4, and TSGF can reflect the treatment effect of patients and are of great importance to efficacy assessment.

Effects of Neoadjuvant Chemotherapy in Ovarian Cancer Patients With Different Germline BRCA1/2 Mutational Status: A Retrospective Cohort Study.

BackgroundWhether neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) against primary debulking surgery (PDS) has a differential effect on prognosis due to Breast Cancer Susceptibility Genes (BRCA)1/2 mutations has not been confirmed by current studies.MethodsAll patients included in this retrospective study were admitted to Qilu Hospital of Shandong University between January 2009 and June 2020, and germline BRCA1/2 mutation were tested. Patients in stage IIIB, IIIC, and IV, re-staged by International Federation of Gynecology and Obstetrics (FIGO) 2014, were selected for analysis. All patients with NAC received 1-5 cycles of platinum-containing (carboplatin, cisplatin, or nedaplatin) chemotherapy. Patients who received maintenance therapy after chemotherapy were not eligible for this study. All relevant medical records were collected.ResultsA total of 322 patients were enrolled, including 112 patients with BRCA1/2 mutations (BRCAmut), and 210 patients with BRCA1/2 wild-type (BRCAwt). In the two groups, 40 BRCAmut patients (35.7%) and 69 BRCAwt patients (32.9%) received NAC. The progression-free survival (PFS) of BRCAmut patients was significantly reduced after NAC (median: 14.9 vs. 18.5 months; p=0.023); however, there was no difference in overall survival (OS) (median: 75.1 vs. 72.8 months; p=0.798). Whether BRCAwt patients received NAC had no significant effect on PFS (median: 13.5 vs. 16.0 months; p=0.780) or OS (median: 54.0 vs. 56.4 months; p=0.323). Multivariate analyses in BRCAmut patients showed that the predictors of prolonged PFS were PDS (p=0.001), the absence of residual lesions (p=0.012), and FIGO III stage (p=0.020); Besides, PARP inhibitor was the independent predictor for prolonged OS in BRCAmut patients (p=0.000), for BRCAwt patients, the absence of residual lesions (p=0.041) and history of PARP inhibitors (p=0.000) were beneficial factors for OS prolongation.ConclusionsFor ovarian cancer patients with FIGO IIIB, IIIC, and IV, NAC-IDS did not adversely affect survival outcomes due to different BRCA1/2 germline mutational status.

Efficacy and safety of daratumumab in the treatment of advanced light chain amyloidosis

目的回顾性分析晚期轻链（AL）型淀粉样变患者接受达雷妥尤单抗治疗的疗效和安全性。方法纳入20例于2017年1月至2021年3月在北京协和医院接受达雷妥尤单抗治疗的初治或复发难治晚期AL型淀粉样变患者。收集患者治疗前基线临床资料及治疗随访资料，分析患者的血液学、器官缓解情况，预后及不良反应。结果20例患者的中位年龄为62（45～73）岁，男女比例2.3∶1，9例为初治，11例为复发难治，梅奥2004分期为Ⅱ/Ⅲ期。4例患者于第1个疗程死亡，其余16例患者中位接受3（1～10）个疗程化疗。治疗后1个月、3个月及6个月血液学总缓解率均为80％，≥非常好的部分缓解率分别为45％、60％及60％，中位血液学起效时间为13（6～28）d，3个月、6个月及12个月心脏缓解率分别为20％、30％及40％，中位起效时间为91（30～216）d，1年总生存率为48.4％。至末次随访，9例（45％）患者死亡，1个月内死亡率为25％，Ⅲb期患者1个月内死亡率为40％。3级以上血液学不良反应以淋巴细胞减少最为常见，非血液学不良反应主要为输注反应及感染。结论达雷妥尤单抗治疗初治及复发难治晚期AL型淀粉样变可快速诱导高水平的血液学缓解，但Ⅲb期患者仍有较高的早期死亡率。

Systemic Light Chain Amyloidosis across Europe: Key Outcomes from a Retrospective Study of 4500 Patients

Systemic Light Chain Amyloidosis across Europe: Key Outcomes from a Retrospective Study of 4500 Patients

Cardiac Amyloid Reaching for Extended Survival (CARES): Study Design of Two Placebo-Controlled, Double-Blind, Randomized, International Phase 3 Trials Assessing Cael-101 in Patients with Mayo Stage Iiia or Stage IIIb AL Amyloidosis

Cardiac Amyloid Reaching for Extended Survival (CARES): Study Design of Two Placebo-Controlled, Double-Blind, Randomized, International Phase 3 Trials Assessing Cael-101 in Patients with Mayo Stage Iiia or Stage IIIb AL Amyloidosis