Brief Summary
This phase III trial compares the effect of dose-escalated radiation therapy to usual care in patients with locally advanced unresectable pancreatic ductal adenocarcinoma who have received an initial 4-6 months of chemotherapy. Usual care options include additional chemotherapy, observation, or standard lower-dose radiation therapy. These treatments may delay tumor growth but have not been shown to improve survival. Radiation therapy uses high energy X-rays to kill cancer cells and shrink tumors. Dose-escalated radiation therapy involves the precise delivery of higher doses to the tumor, often over a shorter period of time. This trial assesses whether using dose-escalated radiation therapy can prolong survival.
Brief Title
Testing Higher Dose Radiation Therapy for Locally Advanced Pancreatic Cancer
Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate whether dose-escalated radiation therapy (RT) improves 3-year overall survival (OS) compared to standard treatments without dose-escalated RT, in locally advanced pancreatic cancer patients without radiographic progression and with biochemical response after an initial interval of chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate and compare local progression between the two treatment arms. II. To evaluate and compare progression-free survival (PFS) between the two treatment arms.
III. To evaluate and compare chemotherapy-free interval between the two treatment arms.
IV. To evaluate and compare toxicity within and between the two treatment arms.
HEALTH-RELATED QUALITY-OF-LIFE (HRQOL) OBJECTIVES:
I. Primary: To compare Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Total Score at 6 months between the two treatment arms.
II. Secondary: To compare nadir of HRQoL scores over course of study participation between the two treatment arms.
III. Secondary: To evaluate HRQoL scores over time between the two treatment arms.
EXPLORATORY OBJECTIVE:
I. Biospecimen collection for future correlative analyses.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I (STANDARD OF CARE): Patients are assigned to 1 of 3 treatment options per physician's decision.
OPTION 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin (FOLFIRINOX or modified FOLFIRINOX \[mFOLFIRINOX\]) or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin (NALIRIFOX) or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion.
OPTION 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per standard of care during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion.
OPTION 3: Patients undergo observation per standard of care. (It is recommended \[but not required\] that this option only be for patients that have already completed total 6 months chemotherapy pre-randomization.)
Additionally, patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study.
ARM II (DOSE-ESCALATED RADIATION THERAPY): Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluoropyrimidine). After completing dose-escalated RT, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. Additionally, patients undergo blood sample collection, CT, MRI and tumor tissue biopsy throughout the study.
After completion of study treatment, patients are followed up every 3 months for 2 years then annually for 3 years.
I. To evaluate whether dose-escalated radiation therapy (RT) improves 3-year overall survival (OS) compared to standard treatments without dose-escalated RT, in locally advanced pancreatic cancer patients without radiographic progression and with biochemical response after an initial interval of chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate and compare local progression between the two treatment arms. II. To evaluate and compare progression-free survival (PFS) between the two treatment arms.
III. To evaluate and compare chemotherapy-free interval between the two treatment arms.
IV. To evaluate and compare toxicity within and between the two treatment arms.
HEALTH-RELATED QUALITY-OF-LIFE (HRQOL) OBJECTIVES:
I. Primary: To compare Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Total Score at 6 months between the two treatment arms.
II. Secondary: To compare nadir of HRQoL scores over course of study participation between the two treatment arms.
III. Secondary: To evaluate HRQoL scores over time between the two treatment arms.
EXPLORATORY OBJECTIVE:
I. Biospecimen collection for future correlative analyses.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I (STANDARD OF CARE): Patients are assigned to 1 of 3 treatment options per physician's decision.
OPTION 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin (FOLFIRINOX or modified FOLFIRINOX \[mFOLFIRINOX\]) or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin (NALIRIFOX) or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion.
OPTION 2: Patients undergo standard dose radiation therapy once daily for 28 fractions and receive fluorouracil or capecitabine per standard of care during radiation therapy. After completing concurrent chemoradiation, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion.
OPTION 3: Patients undergo observation per standard of care. (It is recommended \[but not required\] that this option only be for patients that have already completed total 6 months chemotherapy pre-randomization.)
Additionally, patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study.
ARM II (DOSE-ESCALATED RADIATION THERAPY): Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluoropyrimidine). After completing dose-escalated RT, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. Additionally, patients undergo blood sample collection, CT, MRI and tumor tissue biopsy throughout the study.
After completion of study treatment, patients are followed up every 3 months for 2 years then annually for 3 years.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Email
Nina.Sanford@UTSouthwestern.edu
Completion Date
Completion Date Type
Estimated
Conditions
Pancreas Cancer
Eligibility Criteria
Inclusion Criteria:
* • At time of enrollment, the patient must have received 4-6 months of active chemotherapy with FOLFIRINOX (8-12 cycles) or NALIRIFOX (8-12 cycles) or gemcitabine/nab-paclitaxel (4-6 cycles) (1 regimen, no sequential chemotherapy). "Active chemotherapy" refers to time on chemotherapy not counting treatment breaks (i.e. if a patient had 1 month of chemotherapy followed by 1 month break, this would count as 1 month chemotherapy). Study registration must occur within 45 days of last day of chemotherapy cycle
* BASELINE PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
* Pathologically (histologically or cytologically) proven diagnosis of pancreatic ductal adenocarcinoma
* Locally advanced unresectable disease (as defined per the National Comprehensive Cancer Network \[NCCN\] guidelines and institutional tumor board review)
* Patients must have baseline pre-chemotherapy scans for staging. Options include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment
* Age ≥ 18 years
* Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
* Baseline CA19-9 with a normal bilirubin level (defined as ≤ 1.2 mg/dl)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN)
* POST PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
* If baseline CA19-9 is elevated (defined as \> 37 u/mL) the post-pre-entry chemotherapy CA19-9 must be less than 37 u/mL or a 50% decline from pre-chemotherapy level with absolute value less than 100u/mL
* If baseline CA19-9 is not elevated (defined as ≤ 37 u/mL) the post-pre-entry chemotherapy CA19-9 must remain ≤ 37 u/mL
* No active duodenal or gastric ulcers
* No direct tumor invasion of the bowel or stomach
* Restaging scans showing at least stable disease (no progression). Options for scans include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment, with restaging CT showing at least stable disease
* Not pregnant and not nursing
* No cardiac condition that was the primary reason for hospitalization in the last 6 months
* New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Exclusion Criteria:
\-
* • At time of enrollment, the patient must have received 4-6 months of active chemotherapy with FOLFIRINOX (8-12 cycles) or NALIRIFOX (8-12 cycles) or gemcitabine/nab-paclitaxel (4-6 cycles) (1 regimen, no sequential chemotherapy). "Active chemotherapy" refers to time on chemotherapy not counting treatment breaks (i.e. if a patient had 1 month of chemotherapy followed by 1 month break, this would count as 1 month chemotherapy). Study registration must occur within 45 days of last day of chemotherapy cycle
* BASELINE PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
* Pathologically (histologically or cytologically) proven diagnosis of pancreatic ductal adenocarcinoma
* Locally advanced unresectable disease (as defined per the National Comprehensive Cancer Network \[NCCN\] guidelines and institutional tumor board review)
* Patients must have baseline pre-chemotherapy scans for staging. Options include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment
* Age ≥ 18 years
* Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
* Baseline CA19-9 with a normal bilirubin level (defined as ≤ 1.2 mg/dl)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN)
* POST PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
* If baseline CA19-9 is elevated (defined as \> 37 u/mL) the post-pre-entry chemotherapy CA19-9 must be less than 37 u/mL or a 50% decline from pre-chemotherapy level with absolute value less than 100u/mL
* If baseline CA19-9 is not elevated (defined as ≤ 37 u/mL) the post-pre-entry chemotherapy CA19-9 must remain ≤ 37 u/mL
* No active duodenal or gastric ulcers
* No direct tumor invasion of the bowel or stomach
* Restaging scans showing at least stable disease (no progression). Options for scans include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment, with restaging CT showing at least stable disease
* Not pregnant and not nursing
* No cardiac condition that was the primary reason for hospitalization in the last 6 months
* New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Exclusion Criteria:
\-
Inclusion Criteria
Inclusion Criteria:
* • At time of enrollment, the patient must have received 4-6 months of active chemotherapy with FOLFIRINOX (8-12 cycles) or NALIRIFOX (8-12 cycles) or gemcitabine/nab-paclitaxel (4-6 cycles) (1 regimen, no sequential chemotherapy). "Active chemotherapy" refers to time on chemotherapy not counting treatment breaks (i.e. if a patient had 1 month of chemotherapy followed by 1 month break, this would count as 1 month chemotherapy). Study registration must occur within 45 days of last day of chemotherapy cycle
* BASELINE PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
* Pathologically (histologically or cytologically) proven diagnosis of pancreatic ductal adenocarcinoma
* Locally advanced unresectable disease (as defined per the National Comprehensive Cancer Network \[NCCN\] guidelines and institutional tumor board review)
* Patients must have baseline pre-chemotherapy scans for staging. Options include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment
* Age ≥ 18 years
* Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
* Baseline CA19-9 with a normal bilirubin level (defined as ≤ 1.2 mg/dl)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN)
* POST PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
* If baseline CA19-9 is elevated (defined as \> 37 u/mL) the post-pre-entry chemotherapy CA19-9 must be less than 37 u/mL or a 50% decline from pre-chemotherapy level with absolute value less than 100u/mL
* If baseline CA19-9 is not elevated (defined as ≤ 37 u/mL) the post-pre-entry chemotherapy CA19-9 must remain ≤ 37 u/mL
* No active duodenal or gastric ulcers
* No direct tumor invasion of the bowel or stomach
* Restaging scans showing at least stable disease (no progression). Options for scans include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment, with restaging CT showing at least stable disease
* Not pregnant and not nursing
* No cardiac condition that was the primary reason for hospitalization in the last 6 months
* New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* • At time of enrollment, the patient must have received 4-6 months of active chemotherapy with FOLFIRINOX (8-12 cycles) or NALIRIFOX (8-12 cycles) or gemcitabine/nab-paclitaxel (4-6 cycles) (1 regimen, no sequential chemotherapy). "Active chemotherapy" refers to time on chemotherapy not counting treatment breaks (i.e. if a patient had 1 month of chemotherapy followed by 1 month break, this would count as 1 month chemotherapy). Study registration must occur within 45 days of last day of chemotherapy cycle
* BASELINE PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
* Pathologically (histologically or cytologically) proven diagnosis of pancreatic ductal adenocarcinoma
* Locally advanced unresectable disease (as defined per the National Comprehensive Cancer Network \[NCCN\] guidelines and institutional tumor board review)
* Patients must have baseline pre-chemotherapy scans for staging. Options include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment
* Age ≥ 18 years
* Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
* Baseline CA19-9 with a normal bilirubin level (defined as ≤ 1.2 mg/dl)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN)
* POST PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:
* If baseline CA19-9 is elevated (defined as \> 37 u/mL) the post-pre-entry chemotherapy CA19-9 must be less than 37 u/mL or a 50% decline from pre-chemotherapy level with absolute value less than 100u/mL
* If baseline CA19-9 is not elevated (defined as ≤ 37 u/mL) the post-pre-entry chemotherapy CA19-9 must remain ≤ 37 u/mL
* No active duodenal or gastric ulcers
* No direct tumor invasion of the bowel or stomach
* Restaging scans showing at least stable disease (no progression). Options for scans include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment, with restaging CT showing at least stable disease
* Not pregnant and not nursing
* No cardiac condition that was the primary reason for hospitalization in the last 6 months
* New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06958328
Org Class
Other
Org Full Name
NRG Oncology
Org Study Id
NRG-GI011
Overall Status
Not yet recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Official Title A Phase III Randomized Trial of Dose Escalated Radiation in Locally Advanced Pancreas Cancer (LAPC) Patients (LAP100)
Primary Outcomes
Outcome Description
OS will be estimated by the Kaplan-Meier method (Kaplan 1958). The 3-year OS estimates between the two arms will be compared using a Z-test. A logistic regression model will be used to analyze the effects of factors, in addition to treatment, including, but not limited to the stratification factor, which may be associated with 3-year OS. The primary hypothesis of improved 3-year OS will be tested with a 1-sided significance level of 0.023.
Outcome Measure
Overall survival (OS)
Outcome Time Frame
assessed up to 3 years
Secondary Outcomes
Outcome Description
Defined as progression of the primary tumor/nodes as determined by Response Evaluation Criteria in Solid Tumors criteria. LP will be estimated by the cumulative incidence method (Kalbfleish 1980), with death as a competing risk, and compared between treatment arms using Gray's test (Gray 1988). The Fine-Gray regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with LP (Fine 1999).
Outcome Time Frame
From randomization to date of failure, date of death (competing event), or last known follow-up date, assessed up to 5 years
Outcome Measure
Local progression (LP)
Outcome Description
Defined as local progression, distant failure, or death due to any cause. PFS will be estimated by the Kaplan-Meier method (Kaplan 1958) and estimates between treatment arms will be compared using the log-rank test (Mantel 1966). The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, which may be associated with PFS (Cox 1972).
Outcome Time Frame
From the date of randomization to the date of first PFS failure or last follow-up for patients without a reported PFS event, assessed up to 5 years
Outcome Measure
Progression-free survival (PFS)
Outcome Description
Defined as the time in months without chemotherapy for locally advanced pancreatic cancer post the initial chemotherapy treatment. Mean CFI will be compared between treatment arms using a Z-test. Regression modeling will be used to analyze the effects of factors, in addition to treatment, which may be associated with CFI.
Outcome Time Frame
From the date of last dose of initial chemotherapy to the date of first dose of second line chemotherapy for progression, assessed up to 5 years
Outcome Measure
Chemotherapy-free interval (CFI)
Outcome Description
The percentage of patients on the dose-escalated radiation therapy arm will be reported
Outcome Time Frame
Up to 1 year
Outcome Measure
Long-term radiation-related ≥ grade 3 adverse events
Outcome Description
The percentage of patients will be compared between the treatment arms using a Z-test.
Outcome Time Frame
Up to 90 days after randomization
Outcome Measure
Incidence of ≥ grade 3 adverse events
Start Date
Start Date Type
Estimated
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Byung-Han Rhieu
Investigator Email
brhieu@montefiore.org
Investigator Sponsor Organization
External
Study Department
Radiation Oncology
Study Division
Cancer Related - Please Specify
Categories Mesh Debug
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Prostate Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Endocrine System Cancers --- NEOPLASMS
Gastrointestinal (GI) Cancers --- NEOPLASMS
Gynecologic Cancers --- NEOPLASMS
Lung & Chest Cancers --- NEOPLASMS
Prostate Cancer --- NEOPLASMS
Endocrine System Cancers --- ENDOCRINE GLAND NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Endocrine System Cancers --- ENDOCRINE SYSTEM DISEASES
Diabetes --- ENDOCRINE SYSTEM DISEASES
Diabetes & Endocrine System --- ENDOCRINE SYSTEM DISEASES
Gastrointestinal (GI) Cancers --- CAPECITABINE
MeSH Terms
PANCREATIC NEOPLASMS
DIGESTIVE SYSTEM NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
ENDOCRINE GLAND NEOPLASMS
DIGESTIVE SYSTEM DISEASES
PANCREATIC DISEASES
ENDOCRINE SYSTEM DISEASES
FLUOROURACIL
IRINOTECAN
LEVOLEUCOVORIN
GLUTAMIC ACID
LEUCOVORIN
OXALIPLATIN
IRINOTECAN SUCROSOFATE
GEMCITABINE
ALBUMIN-BOUND PACLITAXEL
RADIOTHERAPY
ELECTROMAGNETIC RADIATION
CAPECITABINE
SPECIMEN HANDLING
BIOPSY
MAGNETIC RESONANCE SPECTROSCOPY
URACIL
PYRIMIDINONES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
CAMPTOTHECIN
ALKALOIDS
FORMYLTETRAHYDROFOLATES
TETRAHYDROFOLATES
FOLIC ACID
PTERINS
PTERIDINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
GLUTAMATES
AMINO ACIDS, ACIDIC
AMINO ACIDS
AMINO ACIDS, PEPTIDES, AND PROTEINS
AMINO ACIDS, DICARBOXYLIC
EXCITATORY AMINO ACIDS
COENZYMES
ENZYMES AND COENZYMES
COORDINATION COMPLEXES
ORGANIC CHEMICALS
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PACLITAXEL
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
DITERPENES
TERPENES
ALBUMINS
PROTEINS
THERAPEUTICS
ELECTROMAGNETIC PHENOMENA
MAGNETIC PHENOMENA
PHYSICAL PHENOMENA
RADIATION
DEOXYRIBONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES
CLINICAL LABORATORY TECHNIQUES
DIAGNOSTIC TECHNIQUES AND PROCEDURES
DIAGNOSIS
INVESTIGATIVE TECHNIQUES
CYTODIAGNOSIS
CYTOLOGICAL TECHNIQUES
DIAGNOSTIC TECHNIQUES, SURGICAL
SURGICAL PROCEDURES, OPERATIVE
SPECTRUM ANALYSIS
CHEMISTRY TECHNIQUES, ANALYTICAL