Para-Aortic Lymph Nodal Staging & Evaluation of Treatment Outcome by 18F FDG-PET in Advanced Cancer Cervix
Condition: Cancer of Cervix
MeSH terms: Uterine Cervical Neoplasms
Study type: Observational

Summary: 
      18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Imaging has been extensively
      used in the evaluation of various malignancies and is rapidly being recognized as a mandatory
      investigations. 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Imaging has
      also been tried in cervical cancers with excellent results for detection of both pelvic and
      extra-pelvic disease in terms of sensitivity and specificity. Till date, PET Imaging has been
      reported to have highest sensitivity and specificity for detection of disease and treatment
      failures compared to other non-invasive investigations available. Treatment decisions
      (Localized RT Vs Extended RT) will be according to the results of PET Scans. The treatment
      response, outcome and follow-up will be labelled according to the PET Scan results and will
      be directed for treatment accordingly.
    

Detailed description: 
      BACKGROUND AND RATIONALE:

      Carcinoma Cervix is the commonest malignancy and a leading cause of cancer mortality seen in
      Indian women. At Tata Memorial Hospital, Carcinoma Cervix constitutes approximately 10% of
      all cancers (1). Nearly 85% of the patients present with advanced stages (FIGO Stage II/III).
      The main stay of treatment has traditionally been radical radiation therapy with 80-90% of
      patients requiring radiation in their lifetime and over decades the survival rates have
      achieved a plateau of 30 - 55% at 5 years. In patients with advanced stages (stages IIB to
      IVA), 15 - 38% have para-aortic lymph nodal metastases (2). Identification of para-aortic
      nodal status allows modification of radiation therapy fields to include this nodal disease,
      which, because of intestinal morbidity, is not routinely included in the treatment field by
      most of the Radiation Oncologists. Extended field radiation therapy that includes the
      para-aortic nodes is associated with a 31% to 50% 5 year-survival, depending on the location
      and extent of para-aortic nodal metastasis and the likelihood of controlling the pelvic
      disease (3-5) Therefore, in advanced cervical cancer, it has been reported that
      progression-free survival is significantly related to para-aortic lymph node metastasis
      (6-8). In a collective series of Gynecologic Oncology Group protocols, Para aortic nodal
      status was the most significant indication of recurrence (6).

      A number of noninvasive modalities have been used to evaluate the status of para-aortic nodal
      metastasis. The introduction of Computed Tomographic (CT) Scanning in the mid-1970s provided
      a method of para-aortic nodal disease evaluation (9). CT Scanning has been widely used for
      clinical staging, but its sensitivity for nodal metastasis is only 44% (10). In contrast to
      CT, which primarily relies on the morphologic criteria, FDG-PET can non-invasively assess
      metabolic activity in cancers and metastatic lesions. The differentiation capability for
      malignant lesions of FDG-PET is not compromised by using morphologic size criteria. Even
      malignant lesions less than 1 cm in diameter that manifest high FDG uptake can be
      differentiated from nonmalignant tissue by using PET. Therefore, FDG-PET can detect
      metastatic para-aortic lymph nodes in patients with advanced cervical cancer whose lymph
      nodes have not been abnormally enlarged.

      Many published data have previously reported the clinical value of 18F FDG PET for imaging
      the primary tumor, staging the nodal and visceral involvement, and also detecting a recurrent
      disease (11-19). Rose et al. (11) used FDG-PET for evaluating nodal metastasis in locally
      advanced cervical cancer before surgical staging, with a sensitivity of 75% and a specificity
      of 92% to detect the metastases of para-aortic lymph nodes. They found that the accuracy of
      FDG-PET was greater than that of CT in detecting the para-aortic lymph nodal metastasis. In a
      similar series, Wu et al. have reported a sensitivity of 85.7%, a specificity of 94.4%, and
      an accuracy of 92% with FDG PET to detect para-aortic lymph nodal metastasis in patients with
      advanced cervical cancer and negative abdominal CT findings. Grigsby et al. (12) demonstrated
      that FDG-PET detects more abnormal lymph node regions than does CT, and that FDG-PET findings
      are a better predictor of survival than those of CT in patients with cervical cancer.

      Magnetic Resonance Imaging (MRI) has also been reviewed in evaluating both the primary
      disease at cervix and also para-aortic nodal staging. MRI has been recognized as an important
      imaging modality for the management of cervical cancer because of its multiplanar capability,
      distinct tissue contrast characteristics using various pulse sequences, and excellent tissue
      contrast, particularly between tumor and surrounding normal tissues. However, PET findings
      were most often compared to CT results, while MRI is nowadays considered as the modality of
      choice for staging the primary tumor (20,21). Only one study by Narayan et al. has compared
      the respective value of MRI and PET for staging loco-regionally advanced cervical cancer
      (22). Their study found that the primary tumor was similarly detected by the two imaging
      techniques with a sensitivity of 100%. On the other hand, except for small-volume metastases,
      PET had a sufficiently high positive predictive value (91%) in the pelvis and para-aortic
      region, to obviate lymph node sampling. More recent studies have shown that the 3D
      quantitative imaging-based method of tumor size assessment using MRI is highly accurate in
      determining actual tumor size and extent (23-27) and may be superior to clinical palpation in
      predicting local tumor control (23,25,28) Conversely, MRI accuracy was insufficient for nodal
      management. If MRI remains the modality of choice for evaluating the loco-regional status of
      the primary tumor, metabolic imaging i.e FDG PET seems particularly useful for staging, in
      one session, extra pelvic nodal metastases. Thus, PET may have a significant impact on
      treatment decision-making.

      Identification of para-aortic nodal status allows modification of radiation therapy fields to
      include this nodal disease. Stehman et al. previously demonstrated the prognostic importance
      of para-aortic nodal status in locally advanced cervical carcinoma (6). In advanced cervical
      cancer, it has been reported that progression-free survival is significantly related to
      para-aortic lymph node metastasis (6-8). Recent studies have shown a survival benefit in
      patients with positive para-aortic nodes treated by extended-field irradiation and concurrent
      radio-sensitizing chemotherapy (29-31).

      PET is also of great value for optimally confirming a complete remission and detecting a
      recurrence non-invasively in post-treatment follow-up. More recently, positron emission
      tomography (PET) with the glucose analogue, 18 F-fluorodeoxyglucose (FDG) has demonstrated
      promising results in evaluating tumor response and predicting survival after primary
      treatment with radiation therapy or chemotherapy for several tumor types, including
      head-and-neck cancer, breast cancer, seminoma, colorectal cancer, lymphoma, and lung cancer
      (33-40). Recently, Grigsby et al have reported the role of FDG PET in posttherapy
      surveillance monitoring in a series of 75 patients with cervical cancer. They have concluded
      that FDG-PET is a valuable tool to evaluate the response of both at primary and its lymph
      node disease after radiation therapy and chemotherapy and for the Post-Rx surveillance of
      patients to detect asymptomatic recurrence (41).
    

Intervention name(s): PET IMAGING
Intervention type(s): Other
Intervention description(s): PET imaging in cervical cancers to predict, prognosticate outcome in cervical cancers
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients with hisotologically proven cervical cancers with FIGO II-IIIB eligible for the
        study will be invited for the study
      
Keywords: FDG-PET Imaging; Cervical Cancer; Post-treatment evaluation; Para-aortic Nodal Staging; Extended field Radiation; Extended field IMRT