Patterns of response and relapse in chemotherapy of extensive squamous carcinoma of the lung

Summary In a large study of combination chemotherapy for patients with extensive squamous carcinoma of the lung, 44 of 247 patients (18%) achieved>50% regression of tumor mass. The likelihood of response was significantly (and independently) higher for females and for fully ambulatory patients. Bone and liver were the most commonly involved metastatic sites, with documented involvement pretreatment in 32 and 16% of patients, respectively. Recurrence in the ipsilateral hemithorax after radiation therapy was the only clinical evidence of disease in 24% of the patients. There were no significant differences in response rate by individual metastatic sites, or for single compared to multiple sites. The median time to response was 4 weeks, with response noted by 8 weeks in 74%.Clinically evident relapse has occurred in 39. Among these, the primary site was the only clinical site of failure in 14, of whom 7 never received radiation therapy. The brain was the only site of initial failure in 6, only 1 of whom had preexisting evidence of brain involvement. Failure in a single area of previously evident disease or the brain accounted for 74% of recurrences in the responding group. These observations suggest that sequential, planned radiation therapy to sites of previous clinical involvement, together with prophylactic whole-brain radiation, may be of benefit in the drug-responsive subpopulation of patients with extensive disease.     

Routine application of the omental pedicle graft in 50 consecutive patients at risk for sternal wound infection

After cardiac surgery, healing can be delayed by sternal wound infection, particularly if mediastinitis develops. Because of the technical simplicity of omentopexy, we recommend the use during open-heart surgery of an omental pedicle graft in selected cases to prevent postoperative complications. This article describes our experience over a 4-month period (from 30 March 1989 through 2 August 1989) with this technique in 50 consecutive patients at moderate-to-high risk for postoperative sternal and mediastinal problems. The patients included 39 men (78%) and 11 women (22%), whose ages ranged from 22 to 83 years (mean, 55 years). Preoperative risk factors included extreme obesity, 13 patients (26%); chronic obstructive pulmonary disease, 13 patients (26%); diabetes mellitus, 6 patients (12%); obesity and diabetes, 8 patients (16%); and obesity, diabetes, and chronic obstructive pulmonary disease, 3 patients (6%). Operative risk factors included cardiac reoperation involving prolonged surgery, 6 patients (12%); bilateral mammary grafting, 17 patients (34%); and the need for prolonged (greater than 72-hour) mechanical respiratory assistance, 2 patients (4%). Three of the 50 patients (6%) were considered to be at moderate risk due to an increase in nosocomial infections at the time of their surgical procedures. Although the omentopexy itself caused no complications, 5 patients had major complications related to the cardiac procedure. Two of these patients died, for an operative mortality of 4%; death was caused by progressive peritonitis in 1 case and by cardiac tamponade in the other case. At least 2 of the remaining 3 patients withstood localized mediastinal infection and had thereafter an extremely benign postoperative course. We conclude that an omental pedicle graft, placed prophylactically in patients at risk for sternal wound infection, can serve as a valuable adjunct to healing after cardiac surgery.     

Prognostic implications of molecular and immunohistochemical profiles of the Rb and p53 cell cycle regulatory pathways in primary non-small cell lung carcinoma.

PURPOSE: Many studies have highlighted the aberrant expression and prognostic significance of individual proteins in either the Rb (particularly cyclin D1, p16INK4A, and pRb) or the p53 (p53 and p21Waf1) pathways in non-small cell lung cancer. We hypothesize that cumulative abnormalities within each and between these pathways would have significant prognostic potential regarding survival. EXPERIMENTAL DESIGN: Our study population consisted of 106 consecutive surgically resected cases of predominantly early-stage non-small cell lung cancer from the National Cancer Institute-Mayo Clinic series, and assessment of proteins involved both immunohistochemical (cyclin D1, p21Waf1, pRb, p16INK4A, and p53) and mutational analysis (p53) in relationship to staging and survival. RESULTS: Cyclin D1 overexpression was noted in 48% of the tumors, p16INK4A negative in 53%, pRb negative in 17%, p53 immunopositive in 50%, p53 mutation frequency in 48%, and p21(Waf1) overexpression in 47%, none with prognostic significance. Cyclin D1 overexpression in pRb-negative tumors revealed a significantly worse prognosis with a mean survival of 2.3 years (P = 0.004). A simultaneous p53 mutation dramatically reduced the mean survival time to 0.9 years (P = 0.007). Cyclin D1 overexpression with either a p53 mutation or a p53 overexpression was also associated with a significantly poorer prognosis (P = 0.0033 and 0.0063, respectively). CONCLUSIONS: Some cumulative abnormalities in the Rb and p53 pathways (e.g., cyclin D1 overexpression and p53 mutations) significantly cooperate to predict a poor prognosis; however, the complexity of the cell cycle protein interaction in any given tumor warrants caution in interpreting survival results when specific protein abnormalities are taken in isolation.     

Mapping molecular networks using proteomics: a vision for patient-tailored combination therapy.

Mapping tumor cell protein networks in vivo will be critical for realizing the promise of patient-tailored molecular therapy. Cancer can be defined as a dysregulation or hyperactivity in the network of intracellular and extracellular signaling cascades. These protein signaling circuits are the ultimate targets of molecular therapy. Each patient's tumor may be driven by a distinct series of molecular pathogenic defects. Thus, for any single molecular targeted therapy, only a subset of cancer patients may respond. Individualization of therapy, which tailors a therapeutic regimen to a tumor molecular portrait, may be the solution to this dilemma. Until recently, the field lacked the technology for molecular profiling at the genomic and proteomic level. Emerging proteomic technology, used concomitantly with genomic analysis, promises to meet this need and bring to reality the clinical adoption of molecular stratification. The activation state of kinase-driven signal networks contains important information relative to cancer pathogenesis and therapeutic target selection. Proteomic technology offers a means to quantify the state of kinase pathways, and provides post-translational phosphorylation data not obtainable by gene arrays. Case studies using clinical research specimens are provided to show the feasibility of generating the critical information needed to individualize therapy. Such technology can reveal potential new pathway interconnections, including differences between primary and metastatic lesions. We provide a vision for individualized combinatorial therapy based on proteomic mapping of phosphorylation end points in clinical tissue material.     

Contribution of ultrasound in the assessment of nerve diseases

Background and purpose: Recently, ultrasound (US) has been used to assess the peripheral nervous system; however, there is no real study about its possible significant role in routine practice. Our study aims to assess the contribution of US as a routine tool in a neurophysiological laboratory. Methods: The study assesses 130 patients who presented clinical suspicion of peripheral nerve diseases, excluding motor neuron disease, radiculopathy, hereditary and acquired polyneuropathy. All patients were clinically, neurophysiologically and sonographically assessed in the same session by the same neurologist/neurophysiologist. To avoid interpretation bias, two independent and blinded clinicians, different than the examiners performing electrodiagnosis and US, reviewed clinical, neurophysiological and US findings (also data about follow‐up, when available) and classified the contribution of US as follows: Contributive (US had influence on the diagnostic and therapeutic strategies), Confirming (US confirmed the clinical and neurophysiological diagnosis), Non‐Confirming (US findings were normal) and Incorrect (US findings led to incorrect diagnosis). Results: US impacted, namely modified the diagnostic and therapeutic path in 42.3% of cases (55 patients); US had a confirmatory role in 40% (52 patients); US did not confirm clinical and neurophysiological diagnosis in 17.7% (23 cases); no incorrect US findings were observed. Conclusion: US complements neurophysiological assessment even in routine practice, and this confirms the increasing interest in US for a multidimensional evaluation of peripheral nerve system diseases.