Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer

Phase 1

Completed

Conditions: Esophageal Cancer

Interventions: Drug: Durvalumab
Drug: Oxaliplatin
Radiation: Radiotherapy
Drug: Tremelimumab
Drug: 5-fluorouracil (5-FU)
Drug: Capecitabine
Drug: Paclitaxel
Drug: Leucovorin
Drug: Carboplatin
Drug: Docetaxel

Registration Number: NCT02735239

Lead Sponsor: Ludwig Institute for Cancer Research

Brief Summary: This is an open-label, Phase 1/2 study to evaluate the safety of durvalumab (MEDI4736) in combination with oxaliplatin/capecitabine chemotherapy in metastatic/locally advanced oesophageal cancer (OC) and with neoadjuvant chemo(radio)therapy before surgery in operable OC. The immunotherapy will be given for a 4-week period before starting the standard chemo(radio)therapy, continuing durvalumab treatment once the chemotherapy starts. The study will include 2 phases, a safety run-in Phase 1 (Cohorts A1 and A2) and an expansion Phase 2 (Cohorts B, C, C-FLOT, D/D2).

Detailed Description: This is an open-label, Phase 1/2 study to evaluate the safety of immunotherapy in combination with chemo (radio) therapy with the following cohorts:

* Cohorts A1, A2, and B: Oxaliplatin/capecitabine chemotherapy in metastatic/locally advanced oesophageal cancer (OC).

* Cohort C: Neoadjuvant oxaliplatin/capecitabine chemotherapy before surgery in operable OC.

* Cohort C-FLOT: Neoadjuvant 5-fluorouracil (5-FU), leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy before surgery in operable OC.

* Cohort D/D2: Neoadjuvant paclitaxel/carboplatin chemotherapy + radiotherapy before surgery in operable OC.

The immunotherapy will be given for a 4-week period before starting the standard chemo(radio)therapy, continuing durvalumab treatment once the chemotherapy starts for all cohorts except Cohort D.

The study will include 2 phases, a safety run-in Phase 1 (Cohorts A1 and A2) and an expansion Phase 2 (Cohorts B including the higher dose tremelimumab cohort from Cohort A2, C, C-FLOT, and D/D2).

Phase 1 will evaluate the safety of durvalumab alone (Cohort A1) administered before chemotherapy (oxaliplatin + capecitabine) in subjects with metastatic or locally advanced OC. After completion of Cohort A1, Phase 2 in Cohorts C, C-FLOT, and D/D2 will begin, and a safety review will determine whether to explore the tremelimumab + durvalumab combination (Cohort A2).

Phase 2 includes the expansion into Cohorts B, C, C-FLOT, and D/D2. Once Cohort A1 is cleared, there will be concurrent enrollment into Phase 2 expansion for Cohorts C, C-FLOT and D/D2 (subjects with operable OC with neoadjuvant chemotherapy or chemoradiotherapy before surgery) and the tremelimumab dose-escalation phase for Cohort A2 (37.5 mg and 75 mg). Once Cohort A2 is completed, another safety review will determine the dose of tremelimumab to be included in the recommended combination dose (RCD) to start enrollment into the Cohort B (subjects with metastatic/locally advanced OC) expansion phase. Subjects treated at the RCD in Cohort A2 (tremelimumab 75 mg) will be included in Cohort B.

Subjects in Cohorts C, C-FLOT and D/D2 will undergo surgery after completing treatment, and they will be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this is within 3 months of surgery. Subjects in Cohort C-FLOT may receive durvalumab, FLOT, or durvalumab plus FLOT at the discretion of the investigator.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 73

Inclusion Criteria

Histological diagnosis of oesophageal or gastrooesophageal cancer and have not received prior chemotherapy.
- Cohorts A and B - metastatic/locally advanced cancer
- Cohorts C/C-FLOT and D/D2 - deemed suitable for surgery with curative intent
Anticipated lifespan greater than 4 months.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
At the time of day 1 of the study, subjects with brain metastases must be asymptomatic for at least 4 weeks and:
- at least 8 weeks without tumour progression after any whole brain radiotherapy
- at least 4 weeks since craniotomy and resection or stereotactic radiosurgery
- at least 3 weeks without new brain metastases as evidenced by MRI/CT
Adequate normal organ and marrow function. Laboratory parameters for vital functions should be in the normal range. Laboratory abnormalities that are not clinically significant are generally permitted.
Written informed consent obtained from the subject; subject been informed of other treatment options, and able to comply with study requirements.
Age 18 years or older.

Exclusion Criteria

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study.
Participation in another clinical study with an investigational product during the last 4 weeks.
Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction.
Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
History of allogeneic organ transplant.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C, known immunodeficiency or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
Known history of previous clinical diagnosis of tuberculosis.
History of pneumonitis or interstitial lung disease.

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A1: Metastatic/locally advanced OC, Durva + Chemotherapy (Chemo)	Oxaliplatin	Durvalumab (750 mg IV every two weeks \[Q2W\]) was to be given for up to 11 doses. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort A2: Metastatic/locally advanced OC, Durva, Treme + Chemo	Durvalumab	Durvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (37.5 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy	5-fluorouracil (5-FU)	Durvalumab (750 mg IV Q2W) was to be given for up to 6 doses. Two cycles of neoadjuvant 5-fluorouracil (5-FU) (2600 mg/m\^2 24-hr IV), leucovorin (200 mg/m\^2 IV), oxaliplatin (85 mg/m\^2 IV), and docetaxel (50 mg/m\^2 IV) chemotherapy (FLOT) were to be administered before surgery starting on the day of the third dose of durvalumab. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions), FLOT or durvalumab plus FLOT at the discretion of the Investigator once recovered from surgery, provided that this was within 3 months of surgery.
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(radio)therapy	Radiotherapy	Durvalumab (750 mg IV Q2W) was to be given for 2 doses. This was followed by five weekly doses of neoadjuvant paclitaxel (50 mg/m\^2 IV) / carboplatin (AUC 2) IV chemotherapy + radiotherapy (41.4 Gy radiotherapy given over 23 fractions) before surgery. Subjects could receive an additional dose of durvalumab after completion of chemoradiation. In Cohort D2, subjects continued durvalumab for 3 additional doses while receiving chemoradiation. Subjects were to undergo surgery 6 to 8 weeks after completing chemo(radio)therapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.
Cohort A1: Metastatic/locally advanced OC, Durva + Chemotherapy (Chemo)	Durvalumab	Durvalumab (750 mg IV every two weeks \[Q2W\]) was to be given for up to 11 doses. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort A1: Metastatic/locally advanced OC, Durva + Chemotherapy (Chemo)	Capecitabine	Durvalumab (750 mg IV every two weeks \[Q2W\]) was to be given for up to 11 doses. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort A2: Metastatic/locally advanced OC, Durva, Treme + Chemo	Oxaliplatin	Durvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (37.5 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort A2: Metastatic/locally advanced OC, Durva, Treme + Chemo	Tremelimumab	Durvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (37.5 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort A2: Metastatic/locally advanced OC, Durva, Treme + Chemo	Capecitabine	Durvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (37.5 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort B: Metastatic/locally advanced OC, Durva, Treme + Chemo	Durvalumab	Durvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (75 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort B: Metastatic/locally advanced OC, Durva, Treme + Chemo	Tremelimumab	Durvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (75 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort B: Metastatic/locally advanced OC, Durva, Treme + Chemo	Oxaliplatin	Durvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (75 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort B: Metastatic/locally advanced OC, Durva, Treme + Chemo	Capecitabine	Durvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (75 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Cohort C: Operable OC; Durva + Chemo	Oxaliplatin	Durvalumab (750 mg IV Q2W) was to be given for up to 5 doses. Two cycles of neoadjuvant oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy were to be administered before surgery. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.
Cohort C: Operable OC; Durva + Chemo	Durvalumab	Durvalumab (750 mg IV Q2W) was to be given for up to 5 doses. Two cycles of neoadjuvant oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy were to be administered before surgery. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.
Cohort C: Operable OC; Durva + Chemo	Capecitabine	Durvalumab (750 mg IV Q2W) was to be given for up to 5 doses. Two cycles of neoadjuvant oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy were to be administered before surgery. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy	Durvalumab	Durvalumab (750 mg IV Q2W) was to be given for up to 6 doses. Two cycles of neoadjuvant 5-fluorouracil (5-FU) (2600 mg/m\^2 24-hr IV), leucovorin (200 mg/m\^2 IV), oxaliplatin (85 mg/m\^2 IV), and docetaxel (50 mg/m\^2 IV) chemotherapy (FLOT) were to be administered before surgery starting on the day of the third dose of durvalumab. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions), FLOT or durvalumab plus FLOT at the discretion of the Investigator once recovered from surgery, provided that this was within 3 months of surgery.
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy	Oxaliplatin	Durvalumab (750 mg IV Q2W) was to be given for up to 6 doses. Two cycles of neoadjuvant 5-fluorouracil (5-FU) (2600 mg/m\^2 24-hr IV), leucovorin (200 mg/m\^2 IV), oxaliplatin (85 mg/m\^2 IV), and docetaxel (50 mg/m\^2 IV) chemotherapy (FLOT) were to be administered before surgery starting on the day of the third dose of durvalumab. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions), FLOT or durvalumab plus FLOT at the discretion of the Investigator once recovered from surgery, provided that this was within 3 months of surgery.
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy	Leucovorin	Durvalumab (750 mg IV Q2W) was to be given for up to 6 doses. Two cycles of neoadjuvant 5-fluorouracil (5-FU) (2600 mg/m\^2 24-hr IV), leucovorin (200 mg/m\^2 IV), oxaliplatin (85 mg/m\^2 IV), and docetaxel (50 mg/m\^2 IV) chemotherapy (FLOT) were to be administered before surgery starting on the day of the third dose of durvalumab. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions), FLOT or durvalumab plus FLOT at the discretion of the Investigator once recovered from surgery, provided that this was within 3 months of surgery.
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(radio)therapy	Durvalumab	Durvalumab (750 mg IV Q2W) was to be given for 2 doses. This was followed by five weekly doses of neoadjuvant paclitaxel (50 mg/m\^2 IV) / carboplatin (AUC 2) IV chemotherapy + radiotherapy (41.4 Gy radiotherapy given over 23 fractions) before surgery. Subjects could receive an additional dose of durvalumab after completion of chemoradiation. In Cohort D2, subjects continued durvalumab for 3 additional doses while receiving chemoradiation. Subjects were to undergo surgery 6 to 8 weeks after completing chemo(radio)therapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy	Docetaxel	Durvalumab (750 mg IV Q2W) was to be given for up to 6 doses. Two cycles of neoadjuvant 5-fluorouracil (5-FU) (2600 mg/m\^2 24-hr IV), leucovorin (200 mg/m\^2 IV), oxaliplatin (85 mg/m\^2 IV), and docetaxel (50 mg/m\^2 IV) chemotherapy (FLOT) were to be administered before surgery starting on the day of the third dose of durvalumab. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions), FLOT or durvalumab plus FLOT at the discretion of the Investigator once recovered from surgery, provided that this was within 3 months of surgery.
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(radio)therapy	Paclitaxel	Durvalumab (750 mg IV Q2W) was to be given for 2 doses. This was followed by five weekly doses of neoadjuvant paclitaxel (50 mg/m\^2 IV) / carboplatin (AUC 2) IV chemotherapy + radiotherapy (41.4 Gy radiotherapy given over 23 fractions) before surgery. Subjects could receive an additional dose of durvalumab after completion of chemoradiation. In Cohort D2, subjects continued durvalumab for 3 additional doses while receiving chemoradiation. Subjects were to undergo surgery 6 to 8 weeks after completing chemo(radio)therapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(radio)therapy	Carboplatin	Durvalumab (750 mg IV Q2W) was to be given for 2 doses. This was followed by five weekly doses of neoadjuvant paclitaxel (50 mg/m\^2 IV) / carboplatin (AUC 2) IV chemotherapy + radiotherapy (41.4 Gy radiotherapy given over 23 fractions) before surgery. Subjects could receive an additional dose of durvalumab after completion of chemoradiation. In Cohort D2, subjects continued durvalumab for 3 additional doses while receiving chemoradiation. Subjects were to undergo surgery 6 to 8 weeks after completing chemo(radio)therapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.

Primary Outcome Measures

Name	Time	Method
Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs)	up to 1 year	Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 110 days after the last dose of study treatment. Treatment-emergent AEs were those that occurred or worsened after administration of the first dose of study treatment. In Cohorts A1, A2 and B, 12, 5 and 7 subjects, respectively, were monitored for dose limiting toxicities (DLTs) during the first 10 weeks of treatment (DLT evaluation period).
Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)	up to 1 year	Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), and in Cycles 1, 3, 5 and 6 in Cohorts A1, A2 and B. In the other cohorts, tumor response was assessed at baseline, post-surgery and 14 days after the last dose. In Cohorts C-FLOT and D, an additional assessment was done prior to surgery and in Cohorts C and D, an additional assessment was done in Cycle 3. Per irRECIST, measurable lesions are categorized as follows: Immune-related Complete Response (irCR): Complete disappearance of all target lesions; Immune-related Partial Response (irPR): ≥ 30% decrease from baseline in the Total Measurable Tumor Burden (TMTB); Immune-related Progressive Disease (irPD): ≥ 20% increase from nadir in TMTB; Immune-related Stable Disease (irSD): not meeting above criteria; irNon-CR/Non-PD: irNon-CR/Non-PD is preferred over SD when no lesions can be measured.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)	Up to 23 weeks	Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), and in Cycles 1, 3, 5 and 6 in Cohorts A1, A2 and B. Per irRECIST, measurable lesions are categorized as follows: irCR: Complete disappearance of all target lesions; irPR: ≥ 30% decrease from baseline in the Total Measurable Tumor Burden (TMTB); irPD: ≥ 20% increase from nadir in TMTB; irSD: not meeting above criteria; irNon-CR/Non-PD: irNon-CR/Non-PD is preferred over SD when no lesions can be measured.
Median Progression-free Survival (PFS) by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method	Up to 3 years	Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), and in Cycles 1, 3, 5 and 6 in Cohorts A1, A2 and B. In the other cohorts, tumor response was assessed at baseline, post-surgery and 14 days after the last dose. In Cohorts C-FLOT and D, an additional assessment was done prior to surgery and in Cohorts C and D, an additional assessment was done in Cycle 3. In Cohorts A1, A2 and B, PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression according to irRECIST or to the date of death, if disease progression did not occur. For Cohorts C, C-FLOT and D/D2, PFS is measured from the date of surgery. Per irRECIST, irPD was defined as a ≥ 20% increase from nadir in the TMTB.
Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method	Up to 3 years	After completion of treatment, all subjects were followed for survival every 6 months for up to 3 years from start of treatment. OS was measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up were censored on the date when they were last known to be alive. Per protocol amendment 8.0, all post study follow-up for the collection of survival data was discontinued as of June 30, 2022.
One Year Survival Rate in Subjects With Operable OC	up to 12 months	OS was measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up were censored on the date when they were last known to be alive. Per protocol amendment 8.0, all post study follow-up for the collection of survival data was discontinued as of June 30, 2022.
Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST)	Up to 7months	18F- fluorodeoxyglucose (18F-FDG) PET scans were conducted at baseline and in Cycle 3 in Cohorts C and D, and after completion of therapy in Cohort C-FLOT and D2. Complete metabolic response: 18F-FDG-avid lesions revert to background of normal tissues in which they are located; Partial metabolic response: 30% or greater reduction in measurable tumors; Stable Metabolic Response: no visible change in metabolic activity of tumor; Progressive metabolic disease: increase in intensity or extent of tumor metabolic activity or new sites of activity.