Purpose Fluorodeoxyglucose–positron emission tomography (FDG-PET) has improved target definition in non-small cell lung cancer (NSCLC), but few data exist regarding changes during radiotherapy. The purpose of this study was to quantify changes in FDG-avid tumor volume and examine its potential use in adaptive radiotherapy for tumor dose escalation or normal tissue sparing. Methods and Materials As part of a pilot study, fourteen patients with stage I-III NSCLC underwent FDG-PET-CT prior to radiation (RT) and mid-RT (after 40–50 Gy). Gross tumor volumes (GTVs) were contoured on CT and PET scans obtained before and during RT. 3D conformal RT plans were generated for each patient first using only pre-treatment CT scans. Mid-RT PET volumes were then used to design boost fields. Results Fourteen patients with FDG-avid tumors were assessed. Two patients had a complete metabolic response, two patients had slightly increased FDG-uptake in the adjacent normal tissue. Mid-RT PET scans were useful in 10 remaining patients. Mean decreases in CT and PET tumor volumes were 26% (range: +15% to −75%) and 44% (range:+10% to −100%) respectively. Designing boosts based on mid-RT PET allowed for meaningful dose escalation of 30–102 Gy (mean 58 Gy), or normal tissue complication probability (NTCP) reduction of 0.4–3% (mean 2%) in 5 of 6 patients with smaller, yet residual, tumor volumes. Conclusions Tumor metabolic activity and volume can change significantly after 40–50 Gy of RT. Using mid-RT PET volumes, tumor dose can be significantly escalated or NTCP reduced. Clinical studies evaluating patient outcome after PET-based adaptive radiotherapy are ongoing.

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Late gestation fetal rat hepatocytes can proliferate under defined in vitro conditions in the absence of added mitogens. However, this capacity declines with advancing gestational age of the fetus from which the hepatocytes are derived. The present studies were undertaken to investigate this change in fetal hepatocyte growth regulation. Examination of E19 fetal hepatocyte primary cultures using immunocytochemistry for 5-bromo-2'-deoxyuridine (BrdU) incorporation showed that approximately 80% of these cells traverse S-phase of the cell cycle over the first 48 h in culture. Similarly, 65% of E19 hepatocytes maintained in culture under defined mitogen-free conditions for 24 h showed nuclear expression of proliferating cell nuclear antigen (PCNA). These in vitro findings correlated with a high level of immunoreactive PCNA in immunofluorescent analyses of E19 liver. In contrast, E21 (term) liver showed little immunoreactive PCNA. The in vivo finding was recapitulated by in vitro studies showing that E21 hepatocytes had low levels of BrdU incorporation during the first day in culture and were PCNA negative shortly after isolation. However, within 12 h of plating, E21 hepatocytes showed cytoplasmic staining for PCNA. Although maintained under mitogen-free conditions, PCNA expression progressed synchronously to a nucleolar staining pattern at 24 to 48 h in culture followed by intense, diffuse nuclear staining at 60 h which disappeared by 72 h. This apparently synchronous cell cycle progression was confirmed by studies showing peak BrdU incorporation on the third day in culture. Whereas DNA synthesis by both E19 and E21 hepatocytes was potentiated by transforming growth factor alpha (TGF alpha), considerable mitogen-independent DNA synthesis was seen in hepatocytes from both gestational ages. These results may indicate that fetal hepatocytes come under the influence of an exogenous, in vivo growth inhibitory factor as term approaches and that this effect is relieved when term fetal hepatocytes are cultured.

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