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   Neutrophil Lymph...
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  Table of Contents  
Year : 2021  |  Volume : 58  |  Issue : 7  |  Page : 1-9


Date of Web Publication4-Feb-2022

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How to cite this article:
. Abstracts. Indian J Cancer 2021;58, Suppl S3:1-9

How to cite this URL:
. Abstracts. Indian J Cancer [serial online] 2021 [cited 2022 Dec 3];58, Suppl S3:1-9. Available from:

  Neutrophil Lymphocyte Ratio (NLR) As a Predictive Biomarker in Metastatic Solid Tumor Patients Receiving Immune Checkpoint Inhibitor (ICI) Top

Anuradha Mehta, Muzzamil Shaikh, Sachin Almel, Suparna Rao, Asha Kapadia

Background: Immune Checkpoint Inhibitor (ICI) with programmed-death 1 (PD 1) and programmed-death ligand 1 (PDL 1) inhibitors have emerged as an impressive treatment option for metastatic and advanced solid tumors in recent times and the indications for the same is expanding. However, choosing an appropriate candidate for treatment with Immunotherapy still remains a challenge especially considering the huge cost of treatment. An optimal biomarker for patient selection is the key to this and the search for the same continues. Many biomarkers like PDL1 expression, Tumor mutation burden (TMB) and Micro satellite instability (MSI) have been utilized across various clinical trials.

Neutrophil Lymphocyte ratio (NLR) is a simple and convenient blood based clinical biomarker that is widely available. It is inexpensive, minimally invasive, and reproducible and has been validated in certain oncological settings as both a prognostic and predictive marker. Its clinical relevance is thought to stem from the fact that an elevated peripheral neutrophil count (the numerator for the NLR) is a marker of chronic inflammation which often leads to impaired immunity, whereas conversely the peripheral lymphocyte count (the denominator) is a hallmark of a healthy cytotoxic T-cell (CTL) response.

This study aims to establish the predictive role of NLR in immunotherapy and thus identifying potential therapeutic strategies to treat potentially resistant groups defined by high NLR using a cut off of 5 for NLR.


Primary objectives:

  • To evaluate the relationship of baseline NLR with Overall Response Rate (ORR) i.e. the percentage of patients who have achieved either a partial response (PR) or complete response (CR).

  • To evaluate the relationship of baseline NLR with Clinical Benefit Rate (CBR) i.e. the percentage of patients who have achieved either a partial response (PR) or complete response (CR) or stable disease (SD) for at least 6 months.

Secondary objectives:

  • To assess the toxicity/adverse events with ICI and its relationship with baseline NLR.
  • To assess the correlation of baseline NLR with Progression Free Survival (PFS).
  • To assess the correlation of baseline NLR with the duration on treatment.
  • To assess the relationship of change in NLR while on treatment with outcomes such as ORR, CBR and PFS.

Type of study – Prospective Cohort Study

Inclusion criteria:

  • Patients aged 18 years and above of either sex
  • Patients with an Eastern Cooperative Oncology Group -Performance status (ECOG PS) 0 to 2.
  • Patients diagnosed with metastatic solid tumors and planned for Immune Checkpoint Inhibitor (ICI) therapy alone.

Exclusion criteria:

  • Prior treatment with immune-stimulatory antitumor agents including Immune Checkpoint Inhibitors.
  • Patients with brain metastases.
  • Patients with autoimmune disease, symptomatic interstitial lung disease or those who are on systemic immunosuppression.
  • Patients without any clinical or computed tomography signs of active infection.
  • Patients who are receiving any additional anti-neoplastic therapies concurrently.

Study population and Site location - Metastatic solid tumor patients receiving Immune Checkpoint Inhibitor (ICI) therapy and attending Outpatient department (OPD), day care or In Patient Department (IPD) at P.D Hinduja Hospital.

Study Methodology: The entire study cohort of metastatic solid tumors would be divided into two groups based on baseline NLR into High and Low NLR groups and there would be a minimum of 30 patients in each subgroup.

After obtaining written informed consent - Clinical case history would be collected in a case proforma to record data on patient demographics and other relevant clinical data. NLR would be calculated at baseline and before each cycle. Response assessment would be done after 4-6 cycles of Immunotherapy.

Outcomes would be analyzed – for Response rates, toxicity and survival.

Sample Size - Total of 60 patients (minimum) would be enrolled into the study over period of 24 months

Statistical Analysis

  • Data would be managed and analyzed using SPSS software.
  • Demographic characteristics would be expressed as frequencies and percentages for categorical variables and as medians and means with standard deviations for quantitative variables.
  • Fisher's exact test and Wilcoxon rank-sum test would be used respectively to describe the association of continuous and categorical variables with baseline NLR status. ¥ Univariate logistic regression analyses would be used to describe the association between NLR and response rates, adverse events and the time duration on ICI therapy.
  • Survival curves according to the cut-off values of NLR would be estimated using the Kaplan-Meier method, and differences assessed using the log rank test.
  • Hazard ratios (HRs) and 95 percent confidence intervals for univariate and multivariate models would be computed with the use of Cox proportional-hazards regression models with p-values < 0>

Result: (The study is still recruiting patients prospectively).

Conclusions: NA

  Effect of Multicomponent Self Help Intervention Package (MSHIP) on Functional Performance and Aerobic Capacity among Patients with Cancer Undergoing Chemotherapy: A Pilot Randomized Controlled Trial Top

Athar Javeth, Fatima DSilva, Pritanjali Singh

Background: Functional performance and aerobic capacity plays a vital role in prognosis and influence the quality of life of patients with cancer. Patients with poor functional performance and aerobic capacity tend to have more difficulty in tolerating rigorous treatments for cancer. The aim of this pilot study is to evaluate the effect of Multicomponent Self Help Intervention Package (MSHIP) on functional performance and aerobic capacity of cancer patients undergoing chemotherapy.

Methods: A parallel armed randomized controlled trial was carried out in 20 mixed cancer patients in the age group of 18-60 years who were admitted for the second cycle of chemotherapy. They were screened for inclusion and exclusion criteria and recruited. Baseline assessment was conducted after screening and they were randomly allocated to the intervention or control group using sequentially numbered opaque envelopes (SNOSE) according to computer generated random order. Block randomization confirms the equal number of patients allocated in each group with 1:1 ratio. The primary outcome was functional performance in meters measured by six minute walk distance test and the secondary outcome was aerobic capacity calculated using the formula VO2 Max = 4.948+(0.023X6MWD). Multicomponent Self Help Intervention Package (MSHIP) included home based walking, range of motion (ROM) exercises, pranayama (breathing exercise), activity management and dietary counselling for 6 weeks. Follow up assessment was done at 3 weeks and 6 weeks.

Result: There was a significant difference in the mean scores in baseline scores and post test scores at 3 weeks and 6 weeks of aerobic capacity of experimental group (p=0.015). There was no significant difference in the post test mean scores of functional performance at 3 weeks and 6 weeks of experimental group and control group. There was a significant association between level of education and functional performance and aerobic capacity (p=0.024). There was a significant association between stage of cancer and functional performance and aerobic capacity (p=0.004). Post hoc test revealed that mean functional performance scores and aerobic capacity scores in the stage II and stage IV category patients had higher mean scores than Stage III patients with cancer.

Conclusions: Multicomponent Self Help Intervention Package is effective in improving the functional performance and aerobic capacity of patients with cancer undergoing chemotherapy.

Trial Registration No: CTRI/2021/03/031794 [Registered on: 08/03/2021]

6MWD - Six Minute Walk Distance

  The Real-World Data on Short-Course of ICI Use is Sparse and Merits Exploration Top

George Abraham, Jyoti Bajpai, Noronha V, Senthil Rajappa, Amit Agarwal, Ullas Batra, Naresh Somani, Thirumalairaj Raja, Shekhar Patil, Ashish M Kaushal, Ashish Joshi, Vivek Radhakrishnan, Navneet Singh, Govind Babu, Rohan Tewani, Saphalta Baghmar, Chandragouda Dodagoudar, Ramya Ananthakrishnan, Shashidhara H.P, Vibhor Sharma, Nandini Menon, Vijay Patil, Amit Joshi, Sudeep Gupta, Kumar Prabhash

Method: A multi-centric observational study on the safety and efficacy of ICI in oncology patients between August 2014 to October 2020 involving 1011 patients across 13 centers in India.

Background: The median age was 59 (min 16- max 98) years with male preponderance (77.9%). The predominant cohort received short-course ICI therapy; the median number of cycles were 5 (95% CI 1 – 27) and median duration of therapy was 3 (95% CI 0.5 – 13) months. ICI were used commonly in second and third line setting in our study (66.4%, n=671). Objective response rate (ORR) (complete or partial response) was documented in 254 (25.1%) of the patients, 202 (20.0%) had stable disease and 374 (37.0%) had progressive disease. The clinical benefit rate was present in 456 (45.1%). Among the patients whom ICI was stopped (n=906), the most common reason for cessation of ICI was disease progression (616, 68.0%) followed by logistic reasons like financial constraints (234, 25.82%). With a median follow up of 14.1 (95%CI 12.9-15.3) months, there were 616 events of progression and 443 events of death and the median progression free survival and overall survival were 6.4 (95%CI 5.5-7.3) and 13.6 (95%CI 11.6-15.7) months respectively in the overall cohort. Among the immune related adverse events (irAEs), autoimmune pneumonitis (29, 3.8%) and thyroiditis (24, 2.4%) were common.

Result: Real-world multicentric Indian data predominantly with short-course ICI therapy, has comparable efficacy/safety to international literature with standard ICI therapy.

  Combined Metronomic Chemo-Immunotherapy in Metastatic Carcinoma of Esophagus in Second Line & Beyond Top

Irappa Madabhavi, Swaroop Revannasiddaiah, Malay Sarkar, Pham Nguyen Quy

Background: Approximately 570,000 new cases are diagnosed with esophageal cancer worldwide annually and approximately 510,000 deaths from this disease per year. There are currently no effective second-line treatments for patients who progress on cisplatin and 5-fluorouracil. Esophageal squamous cell carcinomas and adenocarcinomas have proven to be inherently resistant to systemic treatments as a result of histological, molecular and etiological heterogeneity, with limited responses seen after first line therapy.

Methods: We are presenting 3 case reports of 57 year old man, 53 year old man & 47 year old woman who, presented with dysphasia for solid foods, weight loss and dyspepsia since 1 month, 3 months & 1.5 months respectively. Upper gastro oesophageal endoscopy shows ulcerated friable lesion with minimal luminal compromise with biopsy showing poorly differentiated adenocarcinoma (PDAC) and PECT-CT showed FDG avid lesions in gastroesophageal junction, gastric cardia, multiple retroperitoneal lymph nodes and bilateral liver lesions. All 3 were having stage IV disease, with PDAC, squamous cell carcinoma & PDAC respectively. We have started 1st patient on DOX regimen containing Docetaxel, Oxaliplatin and Capecitabine at an interval of 2 weeks and after 4 cycles he was having stable disease in GE junction, liver and slightly increased size of retroperitoneal lymph nodes. Second & 3rd patient was put on Pclitaxel-carboplatil protocol, after 6 cycles both were having partial response & was managed with 6 cycles CAPOX as second line chemotherapy. After 5th & 6th months of second line chemotherapy both patients were having progressive disease.

Result: In view of radiological progression we started him on Injection, Nivolumab 240mg intravenously every 2 weekly along with low dose capecitabine 500mg twice a day. After 4 cycles of treatment his PET-CT showing complete metabolic response in GE junction, liver and retroperitoneal lesions. Second and third patients were also started on the same protocol and both were having partial response. Now we are continuing Nivolumab and low dose capecitabine planned to complete for 2 years.

Conclusions: So to conclude nivolumab along with metronomic chemotherapy with low dose capecitabine was very well tolerated and exhibited antitumor activity in extensively pretreated patient with metastatic esophageal poorly differentiated adenocarcinoma. Additional studies of Nivolumab and metronomic chemotherapy and immuno-immuno combination therapy in these diseases are ongoing.

  Nivolumab in Relapsed/Refractory Hodgkin's Lymphoma: Impact of Modified Dosing in Indian Population Top

Neha Pathak, Raja Pramanik, Sameer Bakhshi, Akash Kumar, Mehar Chand Sharma, Shamim A Shamim, Sudhir Kumar, Sanjay Thulkar, Atul Sharma

Background: Immune check point inhibitors such as nivolumab are changing the treatment paradigm of relapsed/refractory Hodgkin's lymphoma (r/rHL). Data from single arm studies have shown nivolumab to be an effective and safe therapy. Real world data from resource constrained settings are limited.

Methods: A retrospective single centre study evaluated r/rHL patients (pts) who received nivolumab from January 2016 to March 2021.Baseline and treatment (tt) related characteristics were collected. Statistical analysis was performed using STATA v14.1 SE. Kaplan Meier curves were used for progression free survival (PFS) and overall survival (OS) and cox proportional hazards for univariate and multivariate analysis.

Result: 20 pts were analyzed with median follow up of 24 months, Median age 26 years (9-61 range) 14 nodular sclerosis (NS) and 6 mixed cellularity (MC), 30% bulky, 45% extranodal disease, 70% stage III/IV, 65% primary refractory, 45% post ASCT relapsed, 10% post brentuximab at baseline. All had active disease at time of nivolumab tt, details shown in table. Due to financial constraints, only 5 pts got standard (3 mg/kg every 2 weeks), rest had either flat dose (100 mg) or increased interval of administration (monthly/bimonthly). Median PFS of 13.1 month (95% CI 8.33 months, NR) and median OS was not reached. The 2-year PFS and OS rates: 36% (95% CI 15%, 57%) and 85% (95 CI 60%, 94%), respectively. Only NS vs MC histology was predictive of PFS on multivariate analysis (HR 0.1, 95% C.I 0.014-0.766, p =0.026).

Table: Nivolumab therapy characteristics, n=20

Conclusions: Our study shows comparable efficacy and safety even with compromised dosing and schedule of administration of the drug and favourable outcomes for nodular sclerosis histology.

  Covid 19 & Its Impact on HPV Infection - A Pertinent Question Top

Richi Khandelwal, Bhagyalaxmi Nayak

Background: It is clear that there is strong evidence indicating the multi-organ involvement of COVID-19 infection. An impact on the female genital tract remains to be tested. The complete pathogenetic mechanism of SARS Cov 2 infection is still unclear and at present it has not been demonstrated to be present in cervical cytology samples. HIV infection is a known risk factor for HPV infection.

Methods: Considering the similarity between SARS Cov2 and HIV with respect to their molecular structure there might be some interaction of HPV with SARS Cov2 also, but this is a theoretical assumption and without any strong evidence until now. At present, this remains an hypothesis as we are yet to observe implications, if any of Covid infection on HPV prevalence rate. Immunosuppression is seen with SARS Cov2 infection and is likely to be transient, during this time an individual is susceptible to develop other infections and rates of new HPV infection and its persistence can be high in these patients. Therefore, we have developed a hypothesis wherein the impact and correlations SARS Cov 2 infection on HPV infection can be tested. There might be a potential interaction of HPV with SARS Cov2 which at present can only be answered by large observational studies. In this regard we have initiated a study comparing the prevalence of HPV infection among COVID 19 recovered patients with healthy women, to know the effect of Covid 19 on HPV infection and to study the effect of host virus immune response.

Result: Out of the total 500 women studied till now, the prevalence of HPV infection was higher in patients who have had Covid 19 infection - 38.3 % vs 13.6% (p<0>

Conclusions: The overall implication of this study in cervical cancer management in the future might be to have more meticulous screening in patients who have had history of SARS Cov 2 infection in order to detect cervical lesions early. It is an effort not only to expand our knowledge on SARS Cov 2 infection but it may also help in preventing cervical cancer by early detection and treatment if there is any correlation between SARS Cov 2 and HPV infection.

  PD-L1 Tumor Tissue Expression and Its Correlation with Clinical Profile of Patients with Lung and Stomach Cancer- Experience from A Tertiary Care Centre of Eastern India Top

Sindhu Kilaru, Soumya Surath Panda, Lalatendu Moharana, Spoorthy Kolluri, Suma D, Ghanashyam Biswas

Background: Targeted therapies against Programmed Death Ligand 1 (PD-L1) in various tumors expressing them has revolutionized their management in recent years. As there is limited data on PD-L1 expression in various tumors from India, we aimed to study the PD-L1 expression and its correlation with different clinical parameters in patients of lung and stomach cancers from a tertiary care centre in Eastern India.

Methods: All consecutive patients with stage 4 carcinoma lung and stomach were prospectively evaluated for PD-L1 expression in formalin fixed and paraffin embedded tumor tissue specimens using SP-263 AND DAKO 22C3 pharmaDX kits. A PD-L1 expression of >1% was considered positive and correlation with various parameters was performed.

Result: A total of 75 patients (mean age 59.1±13.8 years, 62% males) were evaluated. After excluding 5 patients (due to nonviable tumor tissue for PD-L1 testing), a total of 70 patients were finally analyzed. 69% (48) had adenocarcinoma lung and 31% (22) had stomach cancer. PD-L1 positivity was seen in a total of 28 (40%) patients. Patients with lung cancer had significantly higher PD-L1 positivity rate than those with stomach cancer (50% vs 16.7%, p=0.02). 48.6% of males and 23.8% of females showed PD-L1 positivity. Similarly, 26.7% of those aged <50>50 years showed PD-L1 positivity. There were no statistically significant differences in PD-L1 positivity with respect to gender (p=0.09) and age groups (p=0.3). 13 of the 48 (27%) lung cancer patients had EGFR mutations and none were ALK positive. 61.5% (8 of 13) of EGFR positive and 34.3% (12 of 35) EGFR negative lung cancer patients showed PD-L1 positivity (p=0.5). Similarly, only 3 (13.6%) of the stomach cancer patients were HER2 positive. 33.3% (1 of 3) of HER2 positive and 10.5% (2 of 19) HER2 negative stomach cancer patients were PD-L1 positive (p=0.6).

Conclusions: 50% of adenocarcinoma lung cancer patients and 17% of stomach cancer patients in our cohort showed PD-L1 positivity. There were no significant differences in PD-L1 positivity with respect to age, gender and molecular mutation profile. Further large scale studies are required to study the association of various factors on PD-L1 expression.

  Urothelial Carcinoma Medley with Diversity and Heterogeneity: A Rare Case Report Top

Vidhya Manohar

Background: Urothelial carcinoma is well recognised to show morphological plasticity and differentiation to variant morphological types and heterologous components. Some variants are rare, but some of the subtypes have shown definite implications in prognosis with an aggressive course. The current WHO classification has not only reiterated its importance but has also provided clarification and definite factual points for better categorisation. The advent of recent diagnostic tools and tailored therapeutic implications has further validated the classification. The accurate recognition is vital and a poses real challenge to the pathologist in this scenario. We present to you a case of high grade urothelial carcinoma with diverse and varied differentiation including small cell neuroendocrine carcinoma, adenocarcinoma and sarcomatoid carcinoma with rhabdomyosarcoma and chondrosarcoma as heterologous components

Methods: This is a 76-year old gentleman who presented with persistent haematuria with passage of clots, and was subsequently investigated for a suspected bladder tumour.

He underwent laboratory investigations and imaging; which showed a distended bladder secondary to a soft tissue mass, and an early right hydronephrosis with no distant metastatic deposits identified. He subsequently underwent Magnetic resonance Imaging (MRI) of the bladder which revealed a 120mm, highly vascular bladder mass arising from the anterior wall. It contained solid and cystic areas, and foci suggestive of myxoid change. Radiologically the features were not characteristic of a pure squamous or urothelial carcinoma, however; there were no features to suggest tumour extension outside the confines of the bladder.

The bladder tumour was biopsied via a transurethral approach. Histopathology showed predominantly necrotic debris with ghost outlines of degenerate, tumour cells whose cytology could not be appreciated. Immunohistochemistry was attempted and the rare viable cells and the necrotic cells were focally positive with Chromogranin A, Synaptophysin and pancytokeratin, although a para-nuclear accentuation was not appreciated. A working diagnosis predominantly necrotic tumour with possible, questionable neuroendocrine differentiation was suggested.

Result: The patient subsequently underwent underwent a radical cystoprostatecomy which included an ileal conduit formation.

At cut-up the bladder specimen showed a large polypoid tumour attached to the anterior bladder wall with a relatively thin fleshy stalk and completely filling up the bladder and measuring up to 90mm in maximum dimension. The tumour showed a variegated appearance with visible necrosis. Representative sections were taken from viable looking foci and taking care to include regions of varied morphological appearances.

Histopathological examination of the tumour sections confirmed a partly necrotic tumour with heterogeneous and high grade morphological appearances. There were areas of atypical spindle cells with a fascicular and whorled arrangement, including scattered giant 'bizarre' nuclei and multinucleated forms. There was a focus of cartilaginous differentiation with atypical chondrocytes, and other areas of poorly-differentiated small round cells with high nuclear cytoplasmic ratio, moulded nuclei and high mitotic activity. Elsewhere there were entrapped banal glands of colonic type and atypical glands with pleomorphism within the tumour. The stroma showed an admixture of fibrous and chondromyxoid appearance.

The tumour was infiltrating into muscularis propria (pT2) and showed extensive lymphovascular invasion. There was no invasion into the surrounding structures such as prostate or seminal vesicles. Interestingly, no unequivocal conventional urothelial carcinoma was identified within the tumour, although we noted flat urothelial carcinoma in situ of classical and glandular differentiation. Additionally, the prostate gland showed an incidental small focus of prostatic acinar adenocarcinoma, amounting to Gleason score 6.

Immunoprofile of the tumour showed 55% by proportion of the tumour to be of neuroendocrine morphology with patchy positivity for CD99, CD56 and Synaptophysin. The sarcomatoid areas comprised of 30% by ratio and included both components, with majority being rhabdomyosarcoma. The remaining 5% and 10% were adenocarcinoma and coagulative necrosis.

Conclusions: The 2016 WHO book identifies sarcomatoid variant as one of the poor prognostic variant and has emphasized the importance of providing percentage of each subtype which will dictate further management. The direct role of divergent morphology is still controversial in management decisions1. Although one paper particularly proposed early cystectomy in non-muscle invasive bladder cancer (T1) with sarcomatoid morphology2, the group from MD Anderson3 did not support this approach, however; the National Comprehensive Cancer Network (NCCN) advocates a more rigorous approach in T1 disease.

In another study by Veskimae et al4 tumour with neuroendocrine differentiation beneficial effect was noted with neoadjuvant chemotherapy.

  Comparative Study of Dose-Dense Weekly Paclitaxel in Combination with Carbolatin Versus Conventional 3 Weekly Paclitaxel and Carboplatin in Terms of Efficacy, Tolerance and Toxicity in Neoadjuvant Treatment of Ovarian Cancer Top

Vijayeta Ray, Shahid Ali Siddiqui

Background: Most patients with epithelial ovarian cancer have advanced-stage disease when the diagnosis is established. Taxanes are important agent in the management of patients with advanced ovarian cancer. Following cytoreductive surgery, the current optimal chemotherapeutic approach consists of a platinum compound together with taxanes. Bone marrow suppression and neurotoxicity was a significant problem in the standard regimen which used a higher paclitaxel dose. One of a number of approaches to reduce toxicity has included weekly administration of Paclitaxel. The lower doses and shorter infusion times used with weekly dosing appear to minimize bone marrow suppression and other toxicities associated with standard paclitaxel 3-weekly administration. The dose-dense approach of weekly paclitaxel may also achieve greater efficacy than standard doses every 3 weeks, through more sustained exposure of dividing tumor cells to paclitaxel's cytotoxic and anti-angiogenic effects.

Methods: Comparative study to find out efficacy, tolerance and adverse reactions of dose dense weekly paclitaxel and carboplatin versus conventional 3 weekly paclitaxel and carboplatin in neoadjuvant treatment of ovarian cancer in terms of:

  1. Response to therapy
  2. Acute toxicities
  3. Late toxicities

MATERIALS AND METHODS: It is a prospective randomized trial conducted on outdoor and indoor patients of Department of Radiotherapy and Clinical Oncology , JNMCH, AMU, ALIGARH enrolled in the thesis during the period of October 2018 to July 2020.

Inclusion Criteria:

  • Histologically confirmed ovarian carcinoma
  • Age > 18years
  • Karnofsky performance status of >60
  • Adequate hematologic (Hb>10 gm/dl, WBC>4000/l and platelets >1lakh/microlitre), Renal (serum creatinine <1> function).
  • No previous radiotherapy or chemotherapy
  • Unresectable, non-metastatic disease

Exclusion Criteria:

  • Serious concomitant disease
  • History of any prior or concurrent cancer in the last 5 years
  • Pregnancy or breastfeeding
  • Prior chemotherapy or radiotherapy

Control arm--received Carboplatin administered at a dose of AUC 5 based on the Calvert formula18 or AUC 6 based on a calculated creatinine clearance. Paclitaxel was administered at the dose of 175 mg/m2. The regimen was repeated every 21 days.

Study arm- received Paclitaxel administered at dose of 80mg/m2 weekly with Carboplatin administered at an AUC of 5 three weekly.

Result: Out of a total of 60 patients enrolled in the study, on follow up 42 patients were analysed. The study arm had 22 patients while the control arm had 20 patients. All patients of study arm received a minimum of 9 cycles of weekly paclitaxel with 3 cycles of three weekly carboplatin while all the patients of control arm received a minimum of 3 cycles of each paclitaxel and carboplatin. The efficacy of NAC was evaluated at only one point, because surgery was performed immediately if chemotherapy was found to be effective.

Most of the patients who presented to us at diagnosis were of more than 60 years with 46% in study group and 50% in control arm; while 36% study arm and 30% control arm belonging to 40-60 years age group. Majority of women belonged to the post-menopausal age group (73% in study arm and 90% in the control arm). Also most of the patients were multiparous with 3 or more children. In both the arms majority of patients had a satisfactory to good ECOG status, 64% in study arm and 70% in control arm having ECOG of 0-1; while 36% in study arm and 30% of control arm had ECOG of 2-3.

In the study arm, maximum patients presented with FIGO stage 3 (46%) or stage 2 (27%) disease. While in the control arm maximum presented with stage 3 disease (40%) followed by stage 1c (30%). Maximum detected histology of tumour was serous type in both the arms (46% in study arm and 40% in control arm). 27% in study arm and 20% in control arm were of mixed histology.10% in the control arm also represented unspecified histology.

Majority patients in both the arms had a baseline pre-treatment level of serum CA-125 between 501-1000 U/ml. (55% in study arm and 50% in control arm). The mean CA-125 at diagnosis in the study arm was 1304.5 U/ml (SD-1402.89; 95% CI=1304.5±770.475) with median being 826 U/ml. While in the control arm the mean CA-125 at diagnosis was 1297.3 U/ml with median being 605.5U/ml (SD-1608.23; 95% CI=1297.3±704.842).

Response assessment was done 1 month after completion of last cycle of chemotherapy according to RECIST 1.1 and GCIG criteria.

Complete response was seen in 72.9% of study arm and 30% of control arm patients.13.6% patients in the study arm and 35% in the control arm showed partial response. While 4.5% of study arm and 20% of control arm patients showed progressive disease. Stable disease was seen in 9% of study arm and 15% of control arm patients. The result was significant at p=0.04.

The mean duration of neoadjuvant treatment in the dose dense weekly arm was 136.81 days (SD-6.19; 95% CI=136.81±2.588) with the median duration being 135.5 days. In the conventional 3 weekly arm the mean duration of neoadjuvant treatment was 139.75 days (SD- 7.26; 95% CI=139.75±3.182) with the median being 139.5 days.

The chemotherapy cycle was interrupted due to grade 2 or above adverse effects / toxicities thus resulting in treatment delay in receiving the chemotherapy ccle. Almost every patient in both the arms showed a treatment delay. While in the dose dense weekly study arm 36.4% showed a delay in treatment within 1 week and 63.6% showed a delay of more than 1 week.

In the conventional arm 30% showed delay within 1 week and 70% showed delay of more than 1 week.

The mean time to surgery in the weekly dose dense arm was 70.09 days (SD-8.262; 95% CI=70.09±3.453) with median being 68 days. While in the conventional 3 weekly arm the mean time to surgery was 69.9 days (SD-8.75; 95% CI=69.9±3.839) with median being 66 days.

Acute Toxicity Assessment During Treatment

We evaluated toxicity during treatment at weeks 3,6,9,12,15 and 18 using CTCAE 4.0. All grades individually reported were considered and the average number of patients manifesting that grade were reported.

The onset of anemia in both the arms was seen as early as on week 3 of treatment with majority being grade 1. Grade1 anemia was seen in an average of 77% patients each in the study arm and 85% of control arm. Grade 2 anemia manifested in average 18% patients of study arm and 15% patients of control arm Grade 3 anemia was seen in average 9% patient of study arm. None of the patients of the control arm manifested grade 3 or 4 anemia during treatment.

Neutropenia in study arm manifested as early as week 3 while it began in control arm at week 6. Grade 1 neutropenia was seen in average 9% patients of study arm and 5% patient of control arm. An average of 9% patients in study arm showed grade 2 neutropenia. None of the patients in either arms showed grade 3 or 4 neutropenia.

Thrombocytopenia began as early as on week 3 in study arm while its onset was at week 9 in the control arm. An average of 9% patients in study arm and 5% patient in control arm manifested grade 1 platelet count decrease. Grade 2 thrombocytopenia was seen in average

5% patient each of study and control arms. Grade 3 or 4 thrombocytopnia was not seen in any patient of either arms.

Myalgia began at week 3 in the study arm and week 6 in the control arm.An average of 45% patients of study arm and 30% patients in the control arm manifested grade 1 myalgia. An average of 23% patients in study arm and 10% patients in control arm showed grade 2 myalgia. None of the patients in either arm manifested grade 3 or 4 myalgia.

Dysesthesia onset began at week 3 in the study arm and week 6 in the control arm.Grade 1 dysesthesia was seen in average of 45% patients of study arm and 35% patients of control arm. An average of 14% patients in study arm and 5% patient of control arm manifested grade 2 dysesthesia. None of the patients showed grade 3 or 4 dysesthesia in either of the arms.

Arthralgia onset began at week 3 in the study arm and week 6 in the control arm and it was maximum at week 15 in both the arms. An average of 36% of patients in study arm and 25% patients in control arm manifested grade 1 arthralgia during treatment. Grade 2 arthralgia was seen in average 9% of study arm and 5% of control arm patient.Grade 3 or 4 arthralgia was not seen in any patient of either arms.

On follow up at 1 month, anemia was present in around 90% of patients in both the arms. Grade 1 anemia was seen in 55% patients of both arms while grade 2 anemia was seen in 36% patients of study arm and 35% patients of control arm. Myalgia was seen in all patients of both arms at 1 month post treatment. Grade 1 myalgia was seen in 82% of study arm and 80% patients of control arm. Grade 2 myalgia manifested in 18% of study arm and 20% of control arm patients. Almost all patients also manifested dysesthesia in both the arms. Grade 1 dysesthesia was seen in 77% of study arm and 80% of control arm patients. While 23% study arm and 20% control arm patients presented with grade 2 dysesthesia. Almost all patients of study arm also manifested paraesthesias, grade 1 in 63.6% and grade 2 in 36.4

patients. On the other hand, 90% patients in control arm manifested paraesthesias, grade 1 being 55% and grade 2 being 35% patients.

Conclusions: We found out significant overall response rate with the dose dense regimen and also the toxicities during treatment were tolerable.

We aim to further continue our study to analyse survival outcome effects in the long run, which is the primary end-point of analysis in majority of landmark trials in this perspective.

It can thus be concluded that weekly dose dense paclitaxel with carboplatin is an effective and feasible treatment option in neoadjuvant setting in patients with advanced ovarian cancer with good response rates and acceptable toxicities

  Robust Tumor Immunity by High Dietary Salt is Dependent on NK Cells and Gut Microbiota Top

Zaigham Abbas Rizvi, Rajdeep Dalal, Srikanth Sadhu, Amit Awasthi

Background: Dietary factors such as high salts (NaCl) are known to modulate immune system and gut microbiota thereby contributing to inflammation and autoimmunity. Within immunosuppressive tumor microenvironment this high salt diet (HSD) induced inflammatory response maybe favourable for tumor immunity as shown by recent studies. However, the changes associated with immune system and gut microbiota underlying ameliorative potential of HSD has been poorly described.

Methods: Here, we characterized the immunological response and evaluated the changes in gut microbiota to understand the contribution of immune component and gut microbes in tumor immunity by high salt diet in mouse model.

Result: In the current study, we report that tumor immunity by HSD is NK cells dependent as depletion of NK cells abrogated tumor protection in mouse. Further, HSD induces upregulation of NK cells frequency and cytotoxicity markers. Notably, HSD administration was found to significantly downregulate key checkpoint inhibitors on NK cells especially PD1. When combined with sub-optimal anti-PD1 neutralization, low salt acted as an adjuvant by dramatically suppressing B16 melanoma progression. Interestingly, tumor immunity by HSD was blunted upon gut microbiota depletion and restored by faecal matter transfer (FMT) from HSD mouse. Metagenomic studies revealed dramatic increase in Bifidobacterium relative abundance upon HSD. Remarkably, transfer of Bifidobacterium combined with salt resulted in melanoma regression in microbiota depleted mice.

Conclusions: Together, our results suggest interplay of NK cells and gut microbiota in HSD induced tumor immunity and a potential therapeutic use of salt as an adjuvant in cancer immunotherapy.


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