A Case of Lung Adenocarcinoma with Marked Improvement of Pulmonary Lymphangitic Carcinomatosis by Adding Bevacizumab to Cisplatin and Pemetrexed

A 40-year-old man with a diagnosis of lung adenocarcinoma (cT4N3M1c, stage IVB) experienced worsening of lymphangitic carcinomatosis in the right lung and right pleural effusion after receiving 1 cycle of first-line chemotherapy consisting of cisplatin and pemetrexed. Bevacizumab was thus added from the second cycle of the cisplatin-pemetrexed regimen, leading to a marked improvement in pulmonary lymphangitic carcinomatosis and a decrease in pleural effusion. Subsequently, maintenance therapy consisting of pemetrexed and bevacizumab was continued, successfully leading to long-term progression-free survival. Generally, pulmonary lymphangitic carcinomatosis shows poor prognosis because of poor response to chemotherapy. However, recent studies have been elucidating the role of the vascular endothelial growth factor A (VEGF-A)/VEGF receptor-2 pathway in pulmonary lymphangitic carcinomatosis. Therefore, bevacizumab is expected to be beneficial in the treatment of this pathological condition.

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Efficacy of EGFR-TKI Plus Chemotherapy or Monotherapy as First-Line Treatment for Advanced EGFR-Mutant Lung Adenocarcinoma Patients With Co-Mutations

Frontiers in Oncology ◽

10.3389/fonc.2021.681429 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zhengyu Yang ◽

Ya Chen ◽

Yanan Wang ◽

Shuyuan Wang ◽

Minjuan Hu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

First Generation ◽

Progression Free Survival ◽

Poor Response ◽

Time To Progression ◽

Free Survival ◽

Egfr Mutant ◽

Egfr Tki ◽

Generation Sequencing ◽

Egfr Tkis

BackgroundCo-mutations was associated with poor response to EGFR-TKIs. First-generation EGFR-TKIs combined with chemotherapy was reported to be more effective than TKIs alone in advanced lung adenocarcinoma patients.ObjectiveThis retrospective study aimed to explore whether EGFR-mutant patients with co-mutations can benefit from EGFR-TKIs plus chemotherapy.Patients and MethodsWe retrospectively collected data of 137 EGFR-mutant patients with advanced lung adenocarcinoma who underwent next-generation sequencing in our hospital in 2018. Among them, 96 were treated with EGFR–TKIs alone and 41 received EGFR–TKIs plus chemotherapy. We analyzed the progression-free survival (PFS) of patients with co-mutations using different treatments.ResultsConcurrent TP53 mutations, especially exon 4 and 6, were associated with a markedly shorter time to progression on EGFR-TKI monotherapy (11.4 months vs. 16.6 months, P=0.003), while EGFR–TKIs plus chemotherapy would benefit those patients more (with TP53: 11.4 months vs. 19.1 months, P=0.001, HR=0.407; without TP53: 16.6 months vs. 18.9 months, P=0.379, HR=0.706). The incidence of T790M after resistance was equal in patients treated with different treatments (53% vs. 53%, P=0.985).ConclusionsIn our study, concurrent TP53 mutations were found to be risk factors for EGFR-TKI monotherapy, but TKI combined with chemotherapy could eliminate this heterogeneity.

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A review of the pathology and management of uterine papillary serous carcinoma and correlation with outcome

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200605000-00003 ◽

2006 ◽

Vol 16 (3) ◽

pp. 972-978 ◽

Cited By ~ 7

Author(s):

D. Faratian ◽

A. Stillie ◽

R. M.C. Busby-Earle ◽

V. J. Cowie ◽

H. Monaghan

Keyword(s):

Univariate Analysis ◽

Prognostic Significance ◽

Progression Free Survival ◽

Poor Response ◽

Serous Carcinoma ◽

Uterine Papillary Serous Carcinoma ◽

Local Practices ◽

Response To Chemotherapy ◽

Diagnostic Biopsy ◽

Papillary Serous Carcinoma

Uterine papillary serous carcinoma (UPSC) accounts for 10% of endometrial carcinomas but a higher proportion of deaths due to its aggressive nature and poor response to chemotherapy and radiotherapy. In order to add to the knowledge of UPSC in the literature and to review our local practices, we examined the pathology, medical records, and management of all cases of UPSC (67 patients) treated in South East Scotland over a 10-year period and also evaluated the prognostic significance of the percentage of UPSC in endometrial pipelle and hysterectomy specimens. Although only 63% of initial diagnostic biopsies were reported to contain UPSC, rereview of the cases revealed UPSC in 98.5% of the preoperative biopsies. The percentage of UPSC in the tumors did not affect the outcome. Stage, positive omentum, and treatment with external-beam +/− intracavitary radiotherapy were significantly correlated with overall survival and progression-free survival by univariate analysis, but only stage (P < 0.01) was correlated with outcome on multivariate analysis. Chemotherapy did not affect outcome. UPSC may be difficult to diagnose in preoperative biopsies, particularly when present as part of a mixed tumor. Even a small percentage of UPSC in a diagnostic biopsy or hysterectomy specimen is correlated with a poor prognosis. This study emphasizes the need of a cooperative, prospective study on this distinct uterine carcinoma.

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Multigene profiling to identify clinically relevant actionable mutations in head and neck cancers: An Indian study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e18529 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e18529-e18529

Author(s):

Sateesh S. Kunigal ◽

Shalini Thakur ◽

Yogesh Shivkumar ◽

Sheela M L ◽

Krishna CR ◽

...

Keyword(s):

Head And Neck ◽

Treatment Outcomes ◽

Point Mutations ◽

Progression Free Survival ◽

Poor Response ◽

Standard Of Care ◽

Response To Therapy ◽

Treatment Modalities ◽

Prognostic Indicators ◽

Response To Chemotherapy

e18529 Background: Head and Neck squamous cell carcinoma (HNSCC) represents approximately 5-10% of malignancies worldwide. Despite the advances in treatment modalities there lies a disparity in response, owing to the underlying molecular and genetic make up. In the era of precision medicine, it is important to profile each disease and customise treatment to improve the outcomes by identifying predictive or prognostic indicators at the molecular and genetic level. Methods: 100 patients with HNSCC, diagnosed at our centre from April 2015-17 were profiled by targeted deep sequencing for hotspot mutations in 48 cancer-related genes using Illumina’s TSCAP panel and MiSeq technology. The average coverage across 220 hot spots was greater than 1000X. Data was processed using Strand Avadis NGS. Mutations identified in the tumor were assessed for ‘actionability’ i.e. response to therapy and impact on prognosis. The clinical data for these patients was collected retrospectively and analysed for treatment outcomes with standard therapy. The association of mutations with habits, stage at presentation, poor treatment outcomes and prognosis was also analysed. Results: Somatic variants were detected in 63.1% of cases. Genetic aberrations were identified in major RAS/RAF signalling pathway in 10 % of cases out of which HRAS activating mutations were the most common (n=4). HRAS was co-mutated with PI3KCA (n=3) and PTEN deletions (n=2). Based on the result, Cetuximab was discontinued in 2 patients with metastatic HNSCC. Other targetable mutations included ATM (n=1), STK11 (n=1), RB1 (n=1) and BRAF (n=1). Disruptive and non-disruptive mutations in TP53 alone were found in 43.8% of H&N cancers, varying widely among different histology with variable treatment outcome. Interestingly all metastatic/recurrent patients, with very short progression free survival of 9-12 months (PFS) post Cisplatinum based chemotherapy, were found to have mutated TP53. TP53 was also found to be co- mutated with ATM gene (n=1), an important prognostic marker, indicating poor response to chemotherapy and radiotherapy. The patients with recurrence and poorer prognosis (n =5) showed point mutations in codon regions 173 -273. Conclusions: Indian patients with HNSCC display a wide mutational landscape with specific actionable targets. Although traditional treatment modalities remain the standard of care, specific mutations may be utilised to customise treatment, prognosticate and predict outcomes.

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Anorectal neuroendocrine carcinoma (NEC): Patient characteristics and treatment outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16702 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16702-e16702

Author(s):

Benjamin Edward Ueberroth ◽

Alex John Liu ◽

Thorvardur Ragnar Halfdanarson ◽

Mohamad Bassam Sonbol

Keyword(s):

Surgical Resection ◽

Metastatic Disease ◽

Mayo Clinic ◽

Large Scale ◽

Tumor Resection ◽

Progression Free Survival ◽

Poor Response ◽

Patient Characteristics ◽

Complete Response ◽

Response To Chemotherapy

e16702 Background: There are only a few reports examining the treatment patterns for poorly differentiated rectal/anal NEC. In this study, we sought to report treatment and survival outcomes for patients with NEC of the anus and rectum seen at Mayo Clinic. Methods: We identified patients with a primary NEC of the anus or rectum using Mayo Clinic databases (Minnesota, Arizona, Florida) from the year 2000 to present. NEC identified within polyps on colonoscopy was excluded from this study. Patients’ demographics were compiled. Kaplan Meier analyses were performed to evaluate overall survival (OS) for all patients, as well as subgroups with locoregional disease (LRD) and metastatic disease at diagnosis. Progression free survival (PFS) was also evaluated for patients with LRD treated with chemoradiation therapy (CRT). Results: 38 patients with NEC of the anus/rectum were identified with a median age of 55.5 years. 23 patients (61%) had metastatic disease at diagnosis and 15 (39%) had LRD. The most common site of metastasis was the liver (n = 20). Patients with metastatic disease at presentation had significantly shorter OS compared to patients with LRD (median OS 10.4 vs. 18.9 months, p = 0.039; HR 2.46, 95% CI [1.001-6.050]). 34 total patients received chemotherapy (ORR 11.8%), with platinum + etoposide (EP) being the most common first-line chemotherapy (n = 26). 10 of 15 patients with LRD received CRT (9 with EP and 1 with 5-FU) with median PFS of 6.3 months (95% CI 2.3-16.5 months), a 1-year PFS rate of 20%, and median OS of 18.6 months (95% CI 13.5-23.7 months). 2/10 received induction chemotherapy prior to CRT with 6/10 undergoing primary tumor resection (1 prior to CRT and 5 after CRT). Only 3 CRT patients were living at time of analysis (all underwent surgical resection), 2 without any active disease, 1 who achieved complete response with CRT then suffered recurrence and is still undergoing treatment. Conclusions: NEC of the anus and rectum is an aggressive malignancy with most patients experiencing metastatic disease at presentation and poor response to chemotherapy at all stages. Even those with LRD experience a very poor prognosis with OS of 18.9 months from diagnosis. For LRD, most patients underwent CRT with only a short-lived response (median PFS 6.3 months). Those achieving sustained response also underwent surgical resection. Overall, prognosis is poor for all stages and further study on a large scale is warranted to better characterize this rare, aggressive malignancy.

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Does alopecia predict response to chemotherapy and prognosis in patients with advanced ovarian cancer? A meta-analysis of prospective randomized phase III trials with 5,114 patients of the AGO meta data base.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5553 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5553-5553

Author(s):

Jalid Sehouli ◽

Edibe Erol ◽

Rolf Richter ◽

Alexander Reuss ◽

Christina Fotopoulou ◽

...

Keyword(s):

Ovarian Cancer ◽

Advanced Ovarian Cancer ◽

Progression Free Survival ◽

Poor Response ◽

Favourable Outcome ◽

Phase Iii ◽

Prognostic Impact ◽

Poor Overall Survival ◽

Response To Chemotherapy ◽

Phase Iii Trials

5553 Background: Alopecia is a relevant side effect of chemotherapy. Our aim was to validate and unconfirmed broad patient´s opinion that a low rate of alopecia may predict poor response to chemotherapy and poor overall survival (OS). Methods: Individual patient data analysis of 5114 patients from four prospective randomised phase III trials conducted between 1995 and 2004 to investigate platinum-taxane based chemotherapy regimens in advanced ovarian cancer. Uni- and multivariate analyses were performed adjusted for age, number of cycles, individual trial, residual mass, tumor stage and histology. Results: 5,114 patients with ovarian cancer (OC) were analyzed. Most patients presented with advanced stage FIGO III/IV (87.8%). A median of 6 cycles were applied (range 0-11). Worst alopecia grade was 0 in 2.2%, 1 in 2.7% and 2 in 87.1%. In 8% patients no data about alopecia were documented. Patients with complete alopecia were more likely to achieve remission (OR 2.83, 95% CI 1.68-4.78 for grade 2 compared to grade 0/1) and had favourable progression-free survival of 19.0 months, (95%CI 18,2-19.7) compared to patients with grade 0/1 (13.8, 95%CI 12.2-15.3 and 14.3, 95%CI 10.8-17.8). Median OS was also significantly longer after grade 2 alopecia 48.8 months (95%CI 47.0-50.5), compared to 28.1 months (95%CI 22.3-33.9) and 33.9 months (95%CI24.3-43.6) for grade 0 and 1, respectively. This prognostic impact was not reteined in multivariate analysis. However, onset of alopecia was an independent prognostic factor for OS: patients with complete alopecia after cycle 3 had a favourable outcome compared to patient who experienced alopecia later during therapy (HR 1.22, 95%CI 1.02-1.46) or no alopecia (HR 1.29, 95%CI 0.98-1.70). Conclusions: We could show for the very first time that there is no evidence that the rate of alopecia is associated with the effect of chemotherapy is of any prognostic relevance. The observation that early onset of alopecia is associated with OS should be confirmed.

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How to optimize your set-up for a VATS right upper lobectomy

10.1510/mmcts.2021.058 ◽

2021 ◽

Keyword(s):

Pleural Effusion ◽

Pulmonary Artery ◽

Lung Adenocarcinoma ◽

Histological Analysis ◽

Lobe Bronchus ◽

Superior Pulmonary Vein ◽

Primary Lung Adenocarcinoma ◽

Set Up ◽

The Right ◽

Intercostal Block

A 77-year-old woman with multiple ground-glass opacities, the largest of which measured 21 mm, has a biopsy-proven primary lung adenocarcinoma in her right upper lobe. We performed a 3-port right-sided VATS using the Copenhagen approach. There was no pleural effusion or evidence of pleural metastatic spread. A tumor was identified in the upper lobe. The surrounding lung tissue appeared normal. We performed a multilevel intercostal block using 0.25% levobupivacaine. The inferior pulmonary ligament was divided. The superior pulmonary vein and 2 branches of the pulmonary artery to the right upper lobe were dissected, encircled, and divided using tan reloads of the Endo GIA stapler. The right upper lobe bronchus was dissected, encircled, and divided in a similar fashion using a purple reload of the Endo GIA stapler following a successful test inflation of the lower and middle lobes. The horizontal fissure was completed with further firings of the stapler. Lymph nodes from stations 2, 4, 7, 8, 9, 10, and 11 were sampled and sent separately for histological analysis. There was no parenchymal or stump leak to 20 cm H20 on the test inflation. Hemostasis and pneumostasis were checked and ensured. A single 24 Fr drain was placed in the apex. Hemostasis was complete. The incision was closed in layers.

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Circulating Tumor Cells are Predictive of Poor Response to Chemotherapy in Metastatic gastric cancer

The International Journal of Biological Markers ◽

10.5301/jbm.5000151 ◽

2015 ◽

Vol 30 (4) ◽

pp. 382-386 ◽

Cited By ~ 10

Author(s):

Su Jin Lee ◽

Jeeyun Lee ◽

Seung Tae Kim ◽

Se Hoon Park ◽

Joon Oh Park ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Tumor Cells ◽

Progression Free Survival ◽

Poor Response ◽

Metastatic Gastric Cancer ◽

Negative Group ◽

Free Survival ◽

Positive Group ◽

Response To Chemotherapy

Background The aim of this study was to investigate the impact of number of circulating tumor cells (CTCs) on the treatment outcome for metastatic gastric cancer (GC) following palliative chemotherapy. Methods CTCs were isolated from 7.5 mL of whole blood from 100 patients with metastatic GC by anti-EpCAM antibody coated magnetic particles using the CTC-Profiler (Veridex). Correlations between CTC counts and clinicopathological variables, progression-free survival and overall survival were examined. Results Between January 2010 and August 2010, 100 metastatic GC patients were enlisted. Among 100 patients, 5 or more CTCs (CTC-positive) were detected in 27 of 95 patients (28%). Even though the clinical characteristics of the CTC-positive and CTC-negative groups were not significantly different, the treatment response to cytotoxic chemotherapy in the CTC-positive group was significantly poorer (progressive disease: 23.4% vs. 60.0% in CTC-negative vs. CTC-positive group, respectively; p = 0.004). The median progression-free survival of the CTC-positive group was substantially shorter than that of the CTC-negative group (59 days vs. 141 days; p = 0.004). For overall survival, CTC-positive group had significantly shorter survival than CTC-negative group (median OS, 120 days vs. 220 days; p = 0.030). A multivariate Cox proportional hazards regression model showed that CTC positivity was an independent adverse factor for progression-free survival and overall survival. Conclusions This study suggests CTCs are associated with poor response to chemotherapy in metastatic GC patients.

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EML4-ALK positive lung adenocarcinoma with skeletal muscle metastasis in the right calf which was treatable with lorlatinib after resistance to treatment with alectinib

BMJ Case Reports ◽

10.1136/bcr-2020-240295 ◽

2021 ◽

Vol 14 (4) ◽

pp. e240295

Author(s):

Hironari Matsuda ◽

Munechika Hara ◽

Shin-Ichiro Iwakami ◽

Kazuhisa Takahashi

Keyword(s):

Skeletal Muscle ◽

Lung Adenocarcinoma ◽

Kinase Inhibitor ◽

Stable Condition ◽

Japanese Woman ◽

Alk Rearrangement ◽

Anaplastic Lymphoma ◽

Resistance To Treatment ◽

Alk Positive ◽

The Right

This report concerns a patient with skeletal muscle metastases due to lung adenocarcinoma harbouring an echinoderm microtubule-associated protein-like-4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement, who was successfully treated with lorlatinib after resistance to alectinib. A right lower lobectomy based on a diagnosis of lung adenocarcinoma was performed on a 77-year-old Japanese woman. After 7 months of surgical resection, a mass in the right calf was observed. A fine-needle aspiration biopsy from the mass was performed and the mass was diagnosed as metastatic adenocarcinoma harbouring EML4-ALK rearrangement. Alectinib was administered for 10 months. Then, administration of lorlatinib, an ALK tyrosine kinase inhibitor classified as third generation, was initiated after resistance to treatment with alectinib. After starting treatment with lorlatinib, the gastrocnemius tumour diminished and has maintained a stable condition. Our case suggests that EML4-ALK positive lung adenocarcinoma is treatable with lorlatinib after resistance to treatment with alectinib.

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To assess the role of addition of bevacizumab therapy to carboplatin and paclitaxel as frontline treatment of epithelial ovarian cancer

10.1055/s-0039-1685308 ◽

2016 ◽

Author(s):

Richa Vatsa ◽

Sunesh Kumar ◽

Lalit Kumar

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Disease Progression ◽

Safety Profile ◽

Haematological Toxicity ◽

Progression Free Survival ◽

New Drugs ◽

Secondary Outcome ◽

Vegf Receptor ◽

Persistent Proteinuria

Introduction: Efforts are going on for development of new drugs for epithelial ovarian cancer (EOC). We assessed safety profile of bevacizumab, a VEGF receptor blocking antibody in treatment of EOC. Methods: We assigned women with EOC to carboplatin (area under curve, 5 or 6) and paclitaxel (175 mg/square meter of body-surface area), given every 3 weeks for 6 cycles, or to this regimen plus bevacizumab (15 mg/kilogram body weight), given concurrently every 3 weeks for 5 or 6 cycles and continued for 30 additional cycles. Primary outcome measures was safety profile of bevacizumab and secondary outcome was to see progression free survival (PFS). Results: Out of 30 patients, 10 were in Bevacizuma arm (Arm A) and 20 in conventional chemotherapy arm (Arm B). Haematological toxicity, GI perforation and proteinuria was similar in both. Other toxicities e.g. bleeding complication (p = 0.002) and hypertension (p = 0.04) was more in Arm A. PFS was similar in both arms; 24 months in Arm A and 22 months in Arm B (p = 0.565). 4 (40%) patients in arm A discontinued treatment, two (20%) because of disease progression after PFS of 9 and 6 months, two because of development of toxicity considered to be due to bevacizumab; of which one developed jejenal perforation and disease progression after PFS of 6 months and 1 because of development of persistent proteinuria of grade 3 after 18 months. Conclusion: Bevacizumab therapy does not improve PFS in EOC but increases toxicity spectrum of chemotherapy.

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Predictive Factors of the Responses to Treatment of Mycoplasma pneumoniae Pneumonia

Journal of Clinical Medicine ◽

10.3390/jcm10061154 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1154

Author(s):

Eun Lee ◽

Yun Young Lee

Keyword(s):

Pleural Effusion ◽

Mycoplasma Pneumoniae ◽

Predictive Factors ◽

Respiratory Virus ◽

Clinical Laboratory ◽

Poor Response ◽

Response To Treatment ◽

Slow Response ◽

Response Group ◽

Time Of Admission

The prevalence of refractory Mycoplasma pneumoniae (MP) pneumonia is increasing. The present study aimed to identify the predictive factors of responses to treatment of MP pneumonia in children. A total of 149 children were diagnosed with MP pneumonia, of whom 56 were included in the good response group, 75 children in the slow response group, and 18 children in no response or progression group. Data on the clinical, laboratory, and radiologic features were retrospectively obtained through medical chart reviews. The severity of pneumonia, based on the extent of pneumonic lesions on chest x-ray (adjusted odds ratio (aOR), 10.573; 95% confidence intervals (CIs), 2.303−48.543), and lactate dehydrogenase (LDH) levels (aOR, 1.002; 95% CIs, 1.000–1.004) at the time of admission were associated with slow response to treatment of MP pneumonia. Pleural effusion (aOR, 5.127; 95% CIs, 1.404–18.727), respiratory virus co-infection (aOR, 4.354; 95% CIs, 1.374–13.800), and higher LDH levels (aOR, 1.005; 95% CIs, 1.002–1.007) as well as MP-specific IgM titer (aOR, 1.309; 95% CIs, 1.095–1.564) were associated with no response or progression of MP pneumonia. The area under the curve for the prediction of no or poor response in MP pneumonia using pleural effusion, respiratory virus co-infection, LDH levels, and MP-specific IgM titer at the time of admission was 0.8547. This study identified the predictive factors of responses to treatment of MP pneumonia in children, which would be helpful in establishing a therapeutic plan and predicting the clinical course of MP pneumonia in children.

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