Search

Objectives Immunotherapy with immune checkpoint inhibitors has shown only limited success in the management of metastatic soft tissue sarcoma. Overall response rates (ORR) with single agent pembrolizumab were 18% and median PFS was 18 weeks on the clinical trial SARC028. One strategy to improve the responses to immunotherapy is with stereotactic body radiation therapy (SBRT), which can enhance the antitumor CD8 T cell response through the release of tumor-specific antigens, potentially priming a more diverse class of T cell receptors. Methods This is a phase 0, pilot prospective study taking place at a single center with 2 arms. In Arm A, patients are treated with pembrolizumab 400 mg IV infusion on day 1 of a 42-day cycle. Stereotactic body radiation therapy (SBRT) is delivered in 1-5 fractions starting on C1D15-28 and given every other day. In Arm B, patients who have started an immune checkpoint inhibitor within 60 days are treated with SBRT in addition to the current therapy. Results In this study we outline testing the feasibility of adding SBRT to pembrolizumab. Conclusion The ultimate goal of combination therapy is improved overall response, including tumors not treated with SBRT. This trial can be found registered online: NCT05488366.

Sotorasib is a first-in-class small molecule that irreversibly inhibits KRAS G12C, locking it in an inactive state, inhibiting oncogenic signaling, and inducing a proinflammatory microenvironment. Here, we report the first case of life-threatening hepatitis in a patient with NSCLC shortly after commencing sotorasib, in which biopsy result was consistent with checkpoint inhibitor (CPI) immune-related adverse event, implicating sotorasib as being able to trigger CPI immune hepatitis. Given the large proportion of patients potentially treatable with sequential sotorasib after CPI, coupled with limited trial data, sotorasib-triggered CPI immune-related hepatitis should be considered in patients with sotorasib hepatotoxicity.

Liver metastasis from breast cancer is associated with poor prognosis and is a major cause of early morbidity and mortality. When liver resection is not feasible, minimally invasive directed therapies are considered to attempt to prolong survival. Selective internal radiation therapy (SIRT) with yttrium-90 microspheres is a liver-directed therapy that can improve local control of liver metastases from colorectal cancer. We present a case of a patient with a ductal breast adenocarcinoma, who developed liver and bone metastasis despite extensive treatment with systemic chemotherapies. Following SIRT to the liver, after an initial response, the patient ultimately progressed in the liver after 7 months. Liver tumor histology obtained 20 months after the SIRT intervention demonstrated the presence of the resin microspheres in situ. This case report demonstrates the long-term control that may be achieved with SIRT to treat liver metastases from breast cancer that is refractory to previous chemotherapies, and the presence of microspheres in situ long-term. Keywords: Selective internal radiation therapy, SIRT, Transarterial radioembolization, Liver-directed therapy

Intensity-modulated radiation therapy (IMRT), an innovative treatment option for prostate cancer, has rapidly diffused over the past decade. To inform our understanding of racial disparities in prostate cancer treatment and outcomes, this study compared diffusion of IMRT in African American (AA) and Caucasian American (CA) prostate cancer patients during the early years of IMRT diffusion using the Surveillance, Epidemiology and End Results (SEER)–Medicare linked database. A retrospective cohort of 947 AA and 10,028 CA patients diagnosed with localized prostate cancer from 2002 through 2006, who were treated with either IMRT or non-IMRT as primary treatment within 1 year of diagnoses was constructed. Logistic regression was used to examine potential differences in diffusion of IMRT in AA and CA patients, while adjusting for socioeconomic and clinical covariates. A significantly smaller proportion of AA compared with CA patients received IMRT for localized prostate cancer (45% vs. 53%, p < .0001). Racial differences were apparent in multivariable analysis though did not achieve statistical significance, as time and factors associated with race (socioeconomic, geographic, and tumor related factors) explained the preponderance of variance in use of IMRT. Further research examining improved access to innovative cancer treatment and technologies is essential to reducing racial disparities in cancer care.

Background: With the increasing population of patients with prior mediastinal irradiation, cardiac surgeons will encounter patients with radiation-induced damage to the heart and the great vessels. Awareness of the pathology and the surgical management is essential to provide optimal care for these patients., Methods: Eight patients with radiation-induced heart disease were encountered in the last 10 years. After a brief clinical presentation, the surgical management of radiation-induced heart disease is reviewed., Results: Radiation can affect all the structures in the heart, including the coronary arteries, the valves, and the conduction system. The pericardium is the most commonly involved, and the conduction system is the least involved. Pericardiectomy is quite effective in patients with symptomatic pericardial effusion or constriction. The coronary lesions are located predominantly in the ostial or proximal regions of the epicardial vessels. Percutaneous transluminal coronary angioplasty alone appears to have a high rate of restenosis. Surgical revascularization has good long-term results, and the internal mammary artery should be used if it is satisfactory. The aortic and mitral valves are more commonly involved than the tricuspid and pulmonary valves. Myocardial dysfunction predominantly affects the right ventricle and requires particular attention during cardiopulmonary bypass and in the postoperative period. Restoration of sinus rhythm is essential in view of stiffness of the ventricles. Flexibility in the surgical approach with selective use of thoracotomy will facilitate the surgical procedure in certain patients., Conclusions: Surgeons should be well versed in all the manifestations and the management of radiation-induced heart disease.

Between 1970 and 1982, 126 inferior vena cava (IVC) balloon occlusions were performed for complications of venous thromboembolism (VTE). Forty, or 32%, were in patients with cancer. There were 20 men and 20 women. The average age was 60.8 +/- 2 years. Cancers of the brain, lung, and breast, along with diffuse metastatic disease with unknown primary disease, were equally common and represented 50% of our cases. Indications for IVC occlusion included pulmonary embolus despite anticoagulation (AC); 50% VTE and contraindication to AC, 38%; and complications of AC, 12%. Three patients died from ongoing complications of previous AC. Eight additional patients died of cancer, for a hospital mortality rate of 28%. Twenty-nine patients were discharged an average of 28.4 +/- 4.3 days after IVC balloon occlusion. Twenty of these patients subsequently died of cancer an average of 13 +/- 4.7 months after hospital discharge. Eight patients remain alive, four for more than 4 years. Pulmonary emboli did not occur after balloon occlusion, and there were no balloon complications. Only 4 of 29 discharged patients had mild leg edema. Hunter balloon occlusion of the IVC represents a safe and effective method for managing complications of VTE in patients with cancer. Early hospital discharge is possible, treatment is permanent, and future chemotherapy is not compromised by the need for long-term anticoagulation.

One percent of 2,545 patients undergoing coronary revascularization with the saphenous vein over a 5 year period sustained leg wound complications which necessitated extra care. Fourteen complications were minor and required only drainage, a new antibiotic, and dressing changes. Thirteen major wound complications required wide debridement and, of these, five could be closed only with skin grafts. Eight wounds were infected, two with Staphylococcus aureus and six with mixed gram-negative flora. Ninety-three percent of these wounds were in the thigh. Average weight of patients with leg wound complications was 73.5 +/- 3.5 kg and not different from that of a randomly selected control group (73.8 +/-1.2 kg). However, 40% of the patients were women, a much higher incidence than control (p less than 0.005). Hospital stay increased significantly from 12.1 +/- 0.5 days for the control group to 24 +/- 2.6 days for the group with wound complications (p less than 0.005). Average hospital stay was 33.6 +/- 3.8 days (p less than 0.001) in those patients with major wound complications (estimated hospital cost $9,900). Leg wound complications of saphenous vein harvest are infrequent but serious. Efforts to prevent this complication should include minimal dissection, careful hemostasis, and closure in layers. Development of skin slough, infection, and necrosis necessitating débridement and drainage is a major and expensive complication. Wide excision and direct closure are necessary to minimize hospital stay and reduce the requirement for skin grafting.

The success of total aortic root replacement in conditions such as annuloaortic ectasia and complicated redo surgery has stimulated its use in acute dissection of the ascending aorta. We believe this radical approach is, in most cases, unwarranted, considering the excellent results with valve conservation. From 1970-1978, 20 consecutive patients with acute anterior aortic dissection and aortic insufficiency were operated at Rush-Presbyterian-St. Luke's Medical Center. Only one patient (5%) required reoperation for hemorrhage. The three operative deaths (15%) were associated with right coronary artery disruption, aortic-right atrial fistula and preoperative intrapericardial false lumen rupture. In eight patients, valve resuspension was combined with primary aortic repair and nine with ascending graft interposition, but aortic valve replacement was required in three because of annuloaortic ectasia or tissue friability. One patient treated by primary repair in 1971 underwent successful reoperation for redissection 7 years later (1.4% per patient-year risk of late reoperation), but the remaining 16 patients, followed 2-10 years, remain free of aortic insufficiency or recurrent aneurysm. This experience supports the use of valve reconstruction rather than replacement in most cases of acute anterior dissection of the aorta.

Cryoablation is recognized as a useful modality for diagnostic mapping, as well as for permanent obliteration of arrhythmogenic foci. This technique has been used to eradicate irritable foci at the base of papillary muscles. We report a case of mitral valve dysfunction requiring valve replacement following cryoablation of the posterior papillary muscle. Based on this experience, we caution against extensive cryoablation of papillary muscle tissue because of the possibility of disrupting mitral valve function.

Over a period of 18 years, 191 consecutive patients had interruption of the inferior vena cava with the Hunter-Sessions balloon for complications of deep venous thrombosis and pulmonary embolism. Causes of deep venous thrombosis and pulmonary embolism included the postoperative state (33%), cancer (32%), and stroke (11%). There were 93 females and 98 males; ages ranged from 17 to 90 years (average, 57 years). Indications for placement of the Hunter-Sessions balloon were as follows: contraindication to anticoagulants (33%), anticoagulant complications (24%), pulmonary embolism despite anticoagulants (45%), and others including inferior vena cava thrombus (12%). Sixty-eight percent had clinical phlebitis and 36% had positive venography results. Pulmonary embolism had occurred in 165 patients (86%). It was diagnosed by ventilation-perfusion scanning (75%), angiography (23%), or on clinical grounds (2%) in patients with confirmed deep venous thrombosis. At the time of the procedure 52% were in significant cardiopulmonary distress, and 10% were intubated and on respirators. Transjugular placement was done in 188 patients, and transfemoral placement was performed in three. All All tolerated inferior vena cava interruption. Thirty patients (15%) died while in the hospital an average of 21 days after balloon placement, which was unrelated to the deaths. Follow-up was 45 months. Ninety-four patients are dead, 95 are alive, and the status of two patients is unknown. Twenty-nine of 64 patients (45%) who died after they left the hospital died of cancer. At last follow-up, 75% of patients had legs free of edema and 25% had need for elastic stockings. No malfunction or migration has occurred with the device. No patient had a pulmonary embolism while in the hospital after insertion of the Hunter-Sessions balloon, and no patient died of pulmonary embolism. Late minor pulmonary embolism occurred in three patients.

Intracardiac migration of an intravenous cathether was treated transvenously in 5 patients successfully. Using local anesthesia and fluoroscopic guidance, a bronchoscopy forceps was passed through the right jugular vein to the right atrium and afforded efficient and safe retrieval of the embolus. The direct route to the right atrium provided by the right internal jugular vein and the precise control offerred by the rigid forceps make this the preferred method of retrieval of a transvenous catheter embolus.

Traditional operations to obstruct the IVC are often unsatisfactory because the morbidity and mortality is appreciable: poor risk patients do not tolerate surgical and anesthetic trauma. Furthermore, if the patient is anticoagulated, an operation requires that such desirable treatment be stopped. Ten years ago a study was begun to develop a transvenous method of IVC occlusion in the awake anticoagulated patient. Animal studies were done prior to patient application. A technique was evolved wherein IVC interruption could be accomplished with a balloon bearing catheter inserted through the jugular vein. The balloon was positioned with venography and after inflation held in place by lateral pressure in the distensible IVC. The catheter was then removed, leaving the balloon in position. Balloon occlusion has been used in the management of 60 selected patients since 1970. Twenty-nine patients were simultaneously anticoagulated without complication. Very sick patients tolerated the procedure well. No patient experienced further pulmonary emboli. Nine hospital deaths occurred from a variety of causes, none related to the balloon catheter. Late follow-up shows that the occluding balloon gradually deflates in about 12 months. The remnant has remained stable in all patients, contained in a scar that permanently interrupts the IVC.

Twenty-four patients were operated on for mitral regurgitation secondary to coronary heart disease. Their common features consisted of a history of myocardial infarction, congestive heart failure, coronary occlusive disease, left ventricular dysfunction, low cardiac output, pulmonary hypertension, and increased left ventricular end-diastolic pressure. Fourteen patients were in intractable congestive heart failure at the time of operation. The operative procedures employed consisted of aneurysmectomy in 4 patients; mitral valve replacement (MVR) in 7;MVR and revascularization in 4; MVR and aneurysmectomy in 5;MVR, revascularization, and partial ventricular resection in 3; and MVR with closure of ventricular septal perforation in 1 patient. Six patients died, a hospital mortality of 25%, and only 42% had good results. The degree of associated coronary artery disease and the status of the left ventricular myocardium were the most important prognostic factors.

In a series of 3,206 consecutive coronary artery bypass procedures performed between 1976 and 1981, 89 patients died (2.8% mortality) and 32 patients (1%) suffered major neurological syndromes. Among the latter patients, four distinct groups were identified. Group 1 consisted of 10 patients who remained unresponsive after operation. In Group 2 were 10 patients who awakened after operation but had clinical evidence of focal cerebral infarction. Group 3 included 6 patients who were initially intact neurologically but in whom neurological deficits later developed. In Group 4 were 6 patients who had severe mental aberration but no focal neurological deficits. The incidence of coma or focal deficit occurring without a lucid interval (Groups 1 and 2) was 0.62%, and these patients had a 30% mortality. Causative factors were suspected in 70% of the patients in Groups 1 and 2, and included atheromatous embolism, perioperative hypotension, carotid artery occlusive disease and air embolism. The outcome was poor for unresponsive patients, with 70% dying or remaining comatose, but nearly all of the patients with focal deficits or severe mental aberration demonstrated notable improvement.

Of 4,124 patients undergoing median sternotomy for cardiac operations, 1.8% had sternal wound complications. These included wound drainage, skin separation, unstable sternum, and sternal dehiscence with or without infection. Septicemia and mediastinal abscess were found in all 19 patients who died. Incision and drainage of skin and subcutaneous tissue with frequent changes of dressing or irrigation (Method A) is recommended for those patients with (I) serosanguineous drainage only or (2) a stable sternum and superficial infection without systemic reaction. Surgical débridement of the sternum and mediastinum with reclosure followed by mediastinal irrigation via drainage tubes with 0.5% povidone-iodine solution (Method B) is recommended for patients with (1) a draining, unstable sternum, (2) infection involving the retrosternal space, or (3) infection causing a systemic reaction unresponsive to Method A. None of the eight patients in the latter group with more serious infections died when managed by Method B, and only one had recurrent infection. In contrast, of 28 patients of the latter group not treated with Method B, 11 died of infection-related causes and 13 returned with recurrent infection.

Conventionally, during aortic valve replacement the left ventricle is vented to achieve a dry field, remove air, and prevent ventricular distention. This report demonstrates the feasibility of performing aortic valve replacement without cannulation of either the left ventricle or the left atrium. The technique has been utilized in 54 patients with 1 early death due to pulmonary embolism and 1 late death presumably secondary to ventricular arrhythmias.