A Trial Comparing Intensity Modulated Radiation Therapy (IMRT) With Conventional Radiation Therapy in Stage IIB Carcinoma Cervix
Condition: Cancer of Cervix
MeSH terms: Uterine Cervical Neoplasms
Study type: Observational

Summary: 
      A study to evaluate the efficacy of Intensity Modulated Radiation Therapy (IMRT) as compared
      to Standard Conventional Radiotherapy Alone in the treatment of carcinoma cervix. Concomitant
      Weekly Cisplatin chemotherapy will be given as a routine, which is a standard of care today
      for early stage cervical cancers including stage IIB. The benefits of using IMRT in reducing
      radiation-induced toxicity are well known. Since this treatment modality has not yet been
      validated and studied in a randomized trial setting, the present study is being undertaken.
      The study arm of IMRT has the potential to reduce the toxicities by 15-20%, but is associated
      with labor intense procedure requiring many hospital visits before actual start of treatment.
    

Detailed description: 
      Carcinoma Cervix is the commonest malignancy seen in Indian women and constitutes
      approximately 10% of all cancers at Tata Memorial Hospital (1). It is also the leading cause
      of cancer mortality in India. 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.

      Radiation therapy is usually a combination of external beam and intracavitary brachytherapy.
      External beam radiation includes irradiation of primary tumor and nodal areas of risk. Higher
      Doses of external beam radiation is limited due to normal critical organs namely, small
      bowel, rectum and bladder. A major concern with pelvic radiation is the considerable volume
      of both small bowel and rectum is included in the radiation treatment fields. Unsurprisingly,
      gastrointestinal radiation reactions include diarrhea while late sequelae include small bowel
      obstruction, enteritis and diarrhea are common (2-4). The benefits of multiple fields, high
      energy beams, customized blocking and low fraction sizes are well known (4). Various methods
      have been used to reduce the small bowel complications. Surgical methods include absorbable
      meshes (5), tissue expanders (6) and omentoplasty (7). However, these approaches are not
      feasible in patients undergoing definitive radiation. Apart from small bowel toxicity, late
      rectal and bladder complications are also of a major concern. The clinical manifestations
      vary from mild proctitis, stricture, bleeding ulcers and fistula formation to hemorrhagic
      cystitis requiring cystectomy. Grade III radiation cystitis and proctitis reported are in the
      range of 3-15% with radiation alone.

      Moreover, of late the pattern of practice is increasingly being emphasized on concomitant
      chemo radiation (8,9). The addition of chemotherapy though has no doubt improved the
      survivals, but has also led to increase in normal tissue toxicities. In the RTOG 90-01 and
      92-10 there is alarming increase in the gastro intestinal (35% grade III and grade IV) and
      genitourinary (9% grade III and grade IV).

      The changes in the treatment policies and the toxicities associated with wide pelvic
      radiation therapy demand for better normal tissue sparing radiation techniques or
      radioprotective agents. Three Dimensional Conformal Radiation Therapy (3D-CRT) to some extent
      has successfully achieved some normal tissue sparing. Intensity-modulated radiotherapy (IMRT)
      is an important recent advance in radiation therapy and is at the forefront of Translational
      Research. With 3DCRT the radiation intensity is generally uniform within the radiation portal
      whereas in IMRT the dose intensity within the portal varies with the use of beamlets, thereby
      allows a higher degree of conformation to the tumor than previously possible and allows
      concave isodose profiles to be generated.

      Over last 10 years, IMRT has been successfully used in the treatment of prostate, head and
      neck and brain tumors. IMRT in pelvic radiation has the potential to reduce the dose as well
      as the volume of rectum, bladder and small bowel irradiated significantly and thereby
      translating into a decrease in the incidence and severity, of acute and late
      gastro-intestinal and genito-urinary toxicities. Several dosimetric studies have been
      reported to confirm the role of IMRT in reducing toxicities with pelvic radiation therapy
      (10,11). These dosimetric studies have reported that the volume of small bowel irradiated to
      the prescription dose by a factor of 2 compared with conventional radiation. The average
      volume of bladder and rectum irradiated is also reduced by 23% (12). In our series of 10
      patients treated, IMRT in pelvic radiation therapy apart from reducing the hot spot volumes
      and better conformity index to the target volume, also significantly reduces the volumes of
      high dose regions in small bowel region (by 17%), rectum (by 50-60%) and bladder (by 40-50%)
      [unpublished data]. In another series of early report on outcome of 40 patients treated with
      IMRT to whole pelvis, Arno el al. have demonstrated that there is a significant reduction in
      acute radiation related toxicities, but it is too early to comment on late sequelae since the
      follow-up is short and has concluded that, this novel approach definitely needs to be
      validated in a trial setting. (13)
    

Intervention name(s): IMRT
Intervention type(s): Radiation
Intervention description(s): IMRT in cervical cancers
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients with histologically proven cervical cancers, FIGO Stage IIb eligible for the study
        will be invited for the study
      
Keywords: Cervical Cancer; FIGO STAGE IIB; CHEMORADIATION; Intensity Modulated Radiation Therapy(IMRT); Conventional Radiation Therapy; Cancer of the Cervix; Cervix Cancer