Survival Benefit of Chemotherapy According to 21-Gene Recurrence Score in Young Women with Breast Cancer.

BACKGROUND: Initial trials evaluating Oncotype DX, reported as a recurrence score (RS) from 0 to 100, were not powered to evaluate overall survival, and premenopausal women were underrepresented. The purpose of this study was to explore the benefit of chemotherapy according to RS among younger women eligible for oncotype testing. METHODS: Women aged 40-50, diagnosed with HR-positive, HER2-negative breast cancer between 2010 and 2017 were selected from the National Cancer Database (NCBD). Patients were grouped by age, RS, nodal status, and chemotherapy receipt. Kaplan-Meier curves were used to compare unadjusted overall survival (OS) between the groups, and log-rank tests were used to test for a difference between groups. Cox proportional hazards models were used to examine the association between select factors and OS. RESULTS: A total of 15,422 patients met inclusion criteria, 45.3% of whom received chemotherapy. Median follow-up time was 66.4 (50.6-86.6) months. Patients who received chemotherapy were more likely to have higher-stage and higher-grade tumors, tumors that were PR-negative, and have higher RS (p < 0.001 for all). RS was prognostic for OS regardless of nodal status. After adjustment, chemotherapy was associated with a significant improvement in OS only in the pN1 RS 31-50 subgroup (p = 0.02). CONCLUSIONS: RS retains its prognostic value in younger patients with early stage HR-positive, HER2-negative breast cancer. Chemotherapy survival benefit was limited to patients aged 40-50 with pN1 disease and RS of 31-50. Therefore, chemotherapy decision-making should be especially preference-sensitive in women aged 40-50 with intermediate RS, where it may not provide a survival benefit for many women.

Neoadjuvant Endocrine Therapy Versus Neoadjuvant Chemotherapy in Node-Positive Invasive Lobular Carcinoma.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is often recommended for patients with node-positive invasive lobular carcinoma (ILC) despite unclear benefit in this largely hormone receptor-positive (HR+) group. We sought to compare overall survival (OS) between patients with node-positive ILC who received neoadjuvant endocrine therapy (NET) and those who received NACT. METHODS: Women with cT1-4c, cN1-3 HR+ ILC in the National Cancer Data Base (2004-2014) who underwent surgery following neoadjuvant therapy were identified. Kaplan-Meier curves and Cox proportional hazards modeling were used to estimate unadjusted and adjusted overall survival (OS), respectively. RESULTS: Of the 5942 patients in the cohort, 855 received NET and 5087 received NACT. NET recipients were older (70 vs. 54 years) and had more comorbidities (Charlson-Deyo score ≥ 1: 21.1% vs. 11.5%), lower cT classification (cT3-4: 44.2% vs. 51.0%), lower rates of mastectomy (72.5% vs. 82.2%), lower rates of pathologic complete response (0% vs. 2.5%), and lower rates of postlumpectomy (73.2% vs. 91.0%) and postmastectomy (60.0% vs. 80.8%) radiation versus NACT recipients (all p < 0.001). NACT recipients had higher unadjusted 10-year OS versus NET recipients (57.9% vs. 36.0%), but after adjustment, there was no significant difference in OS between the two groups (p = 0.10). CONCLUSIONS: Patients with node-positive ILC who received NET presented with smaller tumors, older age, and greater burden of comorbidities versus NACT recipients but had similar adjusted OS. While there is evidence from clinical trials supporting efficacy of NET in HR+ breast cancer, our findings suggest the need for further, histology-specific investigation regarding the optimal inclusion and sequence of endocrine therapy and chemotherapy in ILC.

Risk factors for requiring cataract surgery following total body irradiation.

In order to determine the incidence of cataract surgery following total body irradiation (TBI), questionnaires were mailed to 173 surviving patients who had received single fraction TBI for haematological malignancies. All patients had undergone bone marrow transplantation at the Royal Marsden Hospital, Surrey, between 1977 and 1991. Replies were received from 135 patients (78%). Fifty-four patients had required cataract surgery. The probability of requiring surgery for cataract at 2, 5 and 10 years post TBI was 5%, 39% and 58%, respectively. No cataract surgery was performed at less than 2 years after the time of TBI, and 12 years is the longest interval, prior to surgery, recorded so far. From a number of potential risk factors, those found to predict independently for cataract surgery, and their relative risk (RR) factors, were: cranial radiotherapy preceding TBI (RR 4.2 for patients irradiated in year prior to TBI, 3.3 for others irradiated); skull dose (RR 2.3 for patients over 25 years at time of TBI); TBI dose rate (RR 2.1 for dose rate > 3.5 cGy/min). An additional 31 patients (22%) reported the presence of cataracts which had not yet required surgery.

Chemotherapy and radiotherapy for advanced testicular non-seminoma. I. The influence of sequence and timing of drugs and radiation on the appearance of normal tissue damage.

Acute and delayed normal tissue damage has been investigated in 63 advanced stage testicular non-seminoma patients receiving elective involved-field irradiation after chemotherapy and in 53 patients who had chemotherapy given for relapse after prior irradiation. The risk of death from complications due to chemotherapy was 0% and 9.4% (p less than 0.025) in the two groups respectively. Gastro-intestinal damage and/or subcutaneous fibrosis was present in 12.6% and 24.5% of patients respectively, although only three patients have serious persisting disability. In patients receiving 35-45 Gy to the retroperitoneum the incidence of normal tissue damage was 0% and 25% (p less than 0.001), respectively. In addition to the sequence in which chemotherapy and radiotherapy was delivered, the time interval between completion of radiotherapy and start of chemotherapy was important with 6/6 patients receiving drugs within 2 months of irradiation developing fibrosis. Abdominal surgery appeared not to influence the risk of damage. Of nine patients receiving drugs after infradiaphragmatic and supra-diaphragmatic irradiation two died of neutropenic sepsis.

Effect of supplemental dietary glutamine on methotrexate concentrations in tumors.

This study evaluated the effects of supplemental dietary glutamine (GLN) on methotrexate sodium concentrations in tumors and serum of sarcoma-bearing rats following the initiation of methotrexate. After randomization to a GLN diet (+GLN) or GLN-free diet (-GLN), tumor-bearing rats received 20 mg/kg of methotrexate sodium by intraperitoneal injection. The provision of supplemental GLN in the diet increased methotrexate concentrations in tumor tissues at 24 and 48 hours (38.0 +/- 0.20 nmol/g for the +GLN group vs 28.8 +/- 0.10 nmol/g for the -GLN group and 35.6 +/- 0.18 nmol/g for the +GLN group vs 32.5 +/- 0.16 nmol/g for the -GLN group, respectively). Arterial methotrexate levels were elevated only at 48 hours (0.147 +/- 0.007 microns/L for the +GLN group vs 0.120 +/- 0.006 microns/L for the -GLN group). Tumor morphometrics were not different between the groups but significantly greater tumor volume loss was seen even at 24 hours (-2.41 +/- 1.3 cm3 for the +GLN group vs -0.016 +/- 0.9 cm3 for the -GLN group). Tumor glutaminase activity was suppressed in both groups at 48 hours, but more so in the +GLN group (0.94 +/- 0.13 mumol/g per hour for the +GLN group vs 1.47 +/- 0.22 mumol/g per hour for the -GLN group). This study suggests that GLN may have therapeutic as well as nutritional benefit in oncology patients.

The current evaluation of nonpalpable breast lesions.

To understand the suspected low yield of malignant neoplasms from biopsies guided by needle localization, we reviewed 122 biopsies performed from January 1985 to November 1986 at University Hospital and Arkansas Baptist Medical Center, Little Rock. The positive biopsy rates were 3.5% and 10.6%, respectively. After review of these cases, the following guidelines for biopsy were developed: (1) Do not perform a biopsy on a low-density mass less than 1 cm in diameter. (2) Do not perform a biopsy for asymmetric density or questionable mass. (3) Do not perform a biopsy for secondary signs of malignancy such as skin thickening or asymmetric vasculature. (4) Biopsy is indicated for clustered calcifications, a dominant mass greater than 1 cm in diameter, stellate lesions, or interval change from a previous mammogram. These changes resulted in a positive biopsy rate of 15% for the period from November 1986 through April 1987.

Prognostic significance of carcinoembryonic antigen in colorectal carcinoma. Serum levels before and after resection and before recurrence.

The use of carcinoembryonic antigen was evaluated in 425 patients with a mean follow-up of 48 months. The preoperative and postoperative carcinoembryonic antigen levels were predictive of recurrence and survival independent of the tumor stage. In a multivariate regression analysis of age, location, tumor stage, and preoperative and postoperative carcinoembryonic antigen levels, the latter three factors were significant prognostic variables with respect to the adjusted survival. Recurrent disease was found in 42% of patients, excluding patients with stage IV disease. The carcinoembryonic antigen level at recurrence was greater than 5 ng/mL in 79% of the patients and in 89% of the intra-abdominal recurrences. Carcinoembryonic antigen level at recurrence was not predictive of postrecurrence survival except in the subgroup of locoregional disease. The life span in patients with liver and lung metastases was not influenced by carcinoembryonic antigen level at recurrence. Preoperative and postoperative carcinoembryonic antigen levels can indicate a poorer prognostic group of patients with colorectal cancer who may benefit from adjuvant treatment. The carcinoembryonic antigen at recurrence can be used effectively to diagnose intra-abdominal recurrences and project survival after development of local/regional disease.

Nasal septal melanoma.

The controversial issues on management of nasal septal melanoma center around the extent of pretreatment evaluation. Probably the minimum required is a chest radiograph, CBC, and liver function test (Dr. Westbrook). The use of bone scan and CT scans of brain, lungs, and abdomen (Drs. Suen and Medina) is controversial and of little yield. Aside from distant metastasis to the lung, liver, and brain, the regional metastatic spread pattern includes the nodal groups of the buccal, submental, and submandibular areas, with the possibility of bilateral involvement. All consultants agreed that the primary tumor should be treated with a wide local excision; however, there is no agreement as to the extent of nodal groups included in the nodal dissection. No consultant recommended primary septal reconstruction. The use of postoperative radiotherapy in high-dose fractions remains experimental, in the protocol research stage.

Surgical management of advanced scalp cancer.

A series of 53 advanced scalp cancer patients treated with surgery is presented. A review of these patients concludes: 1) local tumor growth--not distant metastasis--is the primary problem; 2) management is based on the tendency of a tumor to spread laterally early in its development with a deep invasion occurring later on; 3) when deep invasion occurs, radical excision and reconstruction is indicated to control the disease; 4) recurrence following adequate local therapy requires a change in treatment modality.

Acute perforations of the sigmoid colon secondary to diverticulitis.

Diverticulitis is a complex disease and demands careful cooperation between physician and surgeons, because although it is a benign disease, the presence of complications makes it potentially lethal. For successful management, knowledge of the treatment in past decades should be integrated with current surgical technics. A retrospective review of forty-one patients with perforated diverticulitis revealed a significant decrease in morbidity and hospital stay for the group of patients undergoing the Hartmann procedure versus the group undergoing the classic three stage approach. In addition, the Hartmann group required fewer additional surgical procedures for drainage of abscesses. In view of these results as well as those of others, we believe that resection is the primary goal of therapy. The two stage approach therefore offers significant decrease in morbidity with acceptable mortality.

Breast masses in young women.

Based on our review we conclude the following concerning breast masses in young women under 30 years of age: (1) Breast masses are nearly always benign. (2) Mammograms are not helpful in most patients. (3) Needle aspiration or needle biopsy is rarely indicated. (4) Excisional biopsy should be performed through a circumareolar or other cosmetic incision. (5) Preparation for frozen section and mastectomy is not indicated. (6) the breast should be reconstructed in layers without drains. (7) Further manifestations of benign disease can be expected in 15 percent of the cases.

Management of airway problems in lung cancer patients using the neodymium-yttrium-aluminum-garnet (Nd-YAG) laser and endobronchial radiotherapy.

This study summarizes our experience in the evolution of a management technique for unresectable or recurrent lung cancer using the neodymium-yttrium-aluminum-garnet (Nd-YAG) laser with high-dose endobronchial brachytherapy. The laser gave good palliation for hemoptysis and obstruction with a low complication rate, and the addition of endobronchial radiotherapy was a useful adjunct for maintaining airway patency. High-dose brachytherapy delivered by the Gammamed IIi remote afterloader proved to be the best method of delivering this treatment.

Primary malignant retroperitoneal tumors. Current management.

Our experience with 16 retroperitoneal tumors seen over a 13 year period has been reported. Patients presented with either an abdominal mass or abdominal pain associated with a large retroperitoneal tumor. Delineation of the tumor is best accomplished with computerized tomography and venacavography. Exploration and resection is possible in most patients. Postoperative radiotherapy and chemotherapy are recommended in most patients. Local recurrence frequently occurs and should be diagnosed early and resected aggressively if found.

Role of breast magnetic resonance imaging in determining breast as a source of unknown metastatic lymphadenopathy.

BACKGROUND: Occult primary breast cancer (OPBC) represents less than 1% of breast cancer. In only a third of cases, mammography identifies a primary tumor. We hypothesized that rotating delivery of excitation off-resonance breast magnetic resonance imaging (MRI) would identify or exclude the breast as a primary site in patients with OPBC. METHODS: In a retrospective review, 10 patients were identified with OPBC in which MRI was performed. Malignant appearing lesions were correlated with histopathologic findings at biopsy or surgery. RESULTS: MRI identified the primary site in 8 of 10 cases as breast (80%), and excluded it in 2 cases. The extent of disease and location was accurately predicted when compared with histopathologic specimen. CONCLUSIONS: As we continue to focus on a cure of early breast cancer, it is imperative that diagnostic images become more sensitive and specific. MRI accurately predicted OPBC in this subset of patients.

Congenital dilatation of the bile ducts.

Our experience with five cases of cystic dilatation of the extrahepatic bile ducts is reported and compared with the literature. The following conclusions have been reached: (1) The etiology of this anomaly is primarily congenital but may involve an acquired component. (2) Diagnosis should be suspected when any of the triad of abdominal pain, right upper quadrant mass, or jaundice is present. (3) The diagnosis can usually be made in infants based on the clinical picture and routine radiologic studies. (4) Retrograde cholangiopancreatography is a useful tool in making the diagnosis in older children and adults. (5) Roux-en-Y choledochocystojejunostomy is the procedure of choice for type I cysts, excision for type II, and choledochocystoduodenostomy for type III.

Surgical injury of the common bile duct.

Review of our experience with twenty-two bile duct injuries and the literature leads us to the following conclusions: (1) Most biliary strictures follow surgery and can be avoided by adequate exposure, accurate dissection, use of hemostatic clips rather than clamps and ties, and the liberal use of operative cholangiography. (2) Injuries diagnosed at the time of surgery should be repaired by end-to-end anastomosis over a T tube if length is adequate or by Roux-en-Y choledochojejunostomy if length is inadequate. (3) The diagnosis of biliary injury should be suspected when jaundice, biliary fistula, or cholangitis occur in the postoperative period. (4) IVC, PTC, ERCP, or fistulography should be used when possible to delineate the site of injury or stricture and assist in planning the operative repair. (5) Surgery should be performed as soon as the diagnosis is made and the patient is in satisfactory condition for operation. (6) Early reoperation may be necessary to establish drainage and prepare for a later definitive procedure. In some cases, definitive repair can be performed this time. (7) Most late strictures should be repaired with a choledochojejunostomy to a defunctionalized limb of jejunum when resection and primary end-to-end repair cannot be accomplished.

Symptomatic nonparasitic liver cysts.

Based on our experience with four cases of liver cysts and review of the literature, the following conclusions are reached: (1) Diagnosis can be established with routine and special radiologic studies. (2) Laparotomy is indicated for patients with symptoms or uncertain diagnosis. (3) Surgical management should be guided by cyst size, location, and content. (4) Definitive surgical treatment is indicated only for cysts larger than 10 cm.

Melanoma today does not require radical surgery.

From this study we conclude that melanoma has a more favorable outcome today than 20 years ago, 2 cm margins around the tumor achieve acceptable survival and local recurrence rates, primary closure is preferred when possible, elective regional node dissection is of questionable value, and further trials are warranted to determine optimal therapy for intermediate thickness melanoma.

Advantages of the Papillon protocol in the preoperative treatment of rectal carcinoma.

Standard treatment for advanced rectal carcinoma currently includes surgery, radiotherapy, and chemotherapy. Although there are theoretic advantages to preoperative irradiation, it is often not performed because of the prolonged delay of surgery and the purported increase in perioperative complications. A pilot study was undertaken at our institution to evaluate a treatment protocol advocated by Dr. Papillon that offers a shorter treatment time and less patient morbidity than conventional preoperative therapy for rectal carcinoma. Twenty patients with rectal cancer underwent the preoperative regimen that consisted of 3,000 cGy delivered in 10 fractions over 12 days with concomitant 5-fluorouracil and mitomycin-C. Complications were acceptable. Local recurrence was lower than in most reported trials, and survival rates were comparable. Additional benefits of the protocol include lower radiation morbidity to the patient and a decreased delay between diagnosis and surgery.