Neoadjuvant Chemotherapy in Cervical Cancer
Condition: Cervix Cancer; Cervical Cancer; Cancer of the Uterine Cervix
MeSH terms: Uterine Cervical Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      Cervical cancer represents the second commonest cancer in women worldwide, with 500,000 new
      cases and 300,000 deaths reported yearly. Among cervical cancer cases, 80% occur in
      developing countries and about 70% are identified as advanced cancer. According to the
      International Federation of Gynecology and Obstetrics (FIGO) staging system, a locally
      advanced cervical cancer includes stage IB2 to IIB.

      Treatment modalities include radical surgery with or without adjuvant radiotherapy (RT),
      Neoadjuvant Chemotherapy (NAC) plus radical hysterectomy with or without adjuvant RT, and
      concomitant chemo radiation. Currently, platinum based concurrent chemoradiotherapy is the
      gold standard for locally advanced cervical carcinoma.

      Neoadjuvant chemotherapy has many advantages: decreasing tumor size making surgery easier
      with improved rate of complete resection, decreased pelvic recurrence rate significantly,
      decreasing rate of parametrial invasion and lymph node metastasis, better brachytherapy
      distribution, minimal radiation toxicity, and 15% absolute increase of 5-year survival.

      This study will evaluate various factors i.e. patient related (Age, Menopausal status, HPV,
      HIV, Comorbidities), Tumor related pathological stages (TNM), grade, lymphovascular
      perineural invasion, lymph nodes, extranodal extension, tumor margins including radial
      margin, type of tumor i.e. Adeno vs squamous, mutation profile and Treatment related factors
      (type of NAC, duration of NAC, no of cycles of NAC).
    

Detailed description: 
      This is a single group prospective study to evaluate factors affecting treatment responses in
      uterine cervical carcinoma. All patients who will be receiving NAC followed by surgery will
      be included and assessed for various defined factors influencing response. Responses will be
      assessed by RECIST 1.1 criteria.

        1. All patients of cervical growth will be evaluated. Initial clinical evaluation, biopsy
           and if positive, HPV DNA status will be done. On confirmation of malignancy further
           staging will be done by FIGO Classification. Imaging will include contrast enhanced
           computed tomography (CECT) abdomen or Magnetic resonance imaging (MRI) pelvis and
           ultrasound (USG) abdomen. Routine blood investigations, chest X-ray (CXR) and
           Electrocardiography (ECG) will be done.

        2. In recruited patients, 3 cycles of NAC consisting of Paclitaxel (175 mg/m2) and
           Carboplatin (AUC5) at 21 day intervals were given.

        3. Adverse reactions if any were recorded as WHO toxicity grades.

        4. Evaluation of response was done after end of 2nd cycle of chemotherapy with clinical
           examination and Imaging (CT/MRI) by RECIST 1.1 criteria.

        5. Response was divided into two groups- 1) Complete/ Partial response 2) Poor response/
           Stable disease/ Progressive disease. Patients with Poor response/ stable disease/
           progressive disease will undergo concurrent chemoradiation (CCRT) while patients with
           partial/complete response will undergo Wertheim's hysterectomy.

        6. After surgery Pathological evaluation will include T, N, M, histological type,
           Lymphovascular invasion (LVI), Perineural invasion (PNI), Depth of Tumor Invasion, Extra
           nodal extension (ENE), Grade, (next generation sequencing (NGS)- Mutation Analysis.

        7. Post operative external pelvic irradiation was given according to Sedlis criteria in
           node negative, margin negative, parametria negative cases.

        8. Follow up Evaluation was done at 1, 3 & 6 months by clinical examination, Biopsy for any
           recurrence and Imaging (CECT or MRI pelvis) at 6 months. Follow up was continued every 3
           months thereof.
    

Intervention name(s): Neoadjuvant chemotherapy
Intervention type(s): Drug
Intervention description(s): doublet of taxane and carboplatin
Other intervention name(s): Paclitaxel and Carboplatin
Intervention MeSH terms: Paclitaxel; Carboplatin
Intervention model: Single Group Assignment
Intervention model description: Patients with locally advanced carcinoma of the uterine cervix were recruited for assessment of clinical and pathological therapeutic response. Multivariate analysis was conducted to predict the independent predictors of response
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: cancer; cervix; neoadjuvant chemotherapy; predictors