Opinion statement
Cancers of the esophagus and gastroesophageal junction (GEJ) are associated with a high mortality rate. In the United States, the incidence of adenocarcinoma of the distal esophagus ...and GEJ is rising at an alarming rate. Decades of investigation have established the impact on survival of neoadjuvant platinum-based chemotherapy as well as chemoradiation for locally advanced tumors. Distant recurrence remains the most common pattern of failure and efforts to improve therapeutic outcome should focus on optimizing systemic therapy. Induction chemotherapy before preoperative chemoradiation and postoperative adjuvant chemotherapy are approaches to intensify systemic therapy delivery and deserve further investigation. The integration of targeted therapies and development of predictive biomarkers to identify subgroups of patients who are likely to benefit will mark the future of neoadjuvant treatment in this disease.
This phase II trial evaluated continuous-infusion cisplatin and fluorouracil (5-FU) with radiotherapy followed by esophagectomy. The objectives of this trial were to determine the complete pathologic ...response rate, survival rate, toxicity, pattern of failure, and feasibility of administering adjuvant chemotherapy in patients with resectable cancer of the esophagus treated with preoperative chemoradiation.
Patients were staged using computed tomography, endoscopic ultrasound, and laparoscopy. The preoperative treatment plan consisted of continuous intravenous infusion of cisplatin and 5-FU and a total dose of 44 Gy of radiation. Esophagogastrectomy was planned for approximately 4 weeks after the completion of chemoradiotherapy. Paclitaxel and cisplatin were administered as postoperative adjuvant therapy.
Forty-two patients were enrolled onto the trial. Of the 39 patients who proceeded to surgery, 29 responded to preoperative treatment: 11 achieved pathologic complete response (CR) and 18 achieved a lower posttreatment stage. Five patients had no change in stage, whereas eight had progressive disease (four with distant metastases and four with increases in the T and N stages). At a median follow-up of 30.2 months, the median survival time has not been reached and the 2-year survival rate is 62%. The median survival of pathologic complete responders has not been reached, whereas the 2-year survival rate of this group is 91% compared with 51% in patients with complete tumor resection with residual tumor (P =.03).
An excellent survival rate, comparable to that of our prior preoperative trial, was achieved with lower doses of preoperative cisplatin and 5-FU concurrent with radiotherapy.
Treatment options are limited for advanced pancreatic cancer progressive after gemcitabine therapy. The vascular endothelial growth factor pathway is biologically important in pancreatic cancer, and ...docetaxel has modest antitumor activity. We evaluated the role of the anti-vascular endothelial growth factor antibody bevacizumab as second-line treatment for patients with metastatic pancreatic cancer.
Patients with metastatic adenocarcinoma of the pancreas who had progressive disease on a gemcitabine-containing regimen were randomized to receive bevacizumab alone or bevacizumab in combination with docetaxel.
Thirty-two patients were enrolled; 16 to bevacizumab alone (Arm A) and 16 to bevacizumab plus docetaxel (Arm B). Toxicities were greater in Arm B with the most common grade 3/4 nonhematologic toxicities including fatigue, diarrhea, dehydration, and anorexia. No confirmed objective responses were observed. At 4 months, 2 of the 16 patients in Arm A and 3 of the 16 patients in Arm B were free from progression. The study was stopped according to the early stopping rule for futility. Median progression-free survival and overall survival were 43 days and 165 days in Arm A and 48 days and 125 days in Arm B. Elevated d-dimer levels and thrombin-antithrombin complexes were associated with decreased survival and increased toxicity.
Bevacizumab with or without docetaxel does not have antitumor activity in gemcitabine-refractory metastatic pancreatic cancer. Baseline and on-treatment d-dimer and thrombin-antithrombin complex levels are associated with increased toxicity and decreased survival.
Most patients diagnosed with head and neck squamous cell carcinoma (HNSCC) will present with locally advanced disease, requiring multimodality therapy. While this approach has a curative intent, a ...significant subset of these patients will develop locoregional failure and/or distant metastases. The prognosis of these patients is poor, and therapeutic options other than palliative chemotherapy are urgently needed. Epidermal growth factor receptor (EGFR) overexpression is an important factor in the pathogenesis of HNSCC, and a decade ago, the EGFR targeting monoclonal antibody cetuximab was approved for the treatment of late-stage HNSCC in different settings. In 2016, the anti-programmed death-1 (PD-1) immune checkpoint inhibitors nivolumab and pembrolizumab were both approved for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy, and in 2019, pembrolizumab was approved for first-line treatment (either as monotherapy in PD-L1 expressing tumors, or in combination with chemotherapy). Currently, trials are ongoing to include immune checkpoint inhibition in the (neo)adjuvant treatment of HNSCC as well as in novel combinations with other drugs in the recurrent/metastatic setting to improve response rates and survival and help overcome resistance mechanisms to immune checkpoint blockade. This article provides a comprehensive review of the management of head and neck cancers in the current era of immunotherapy.
Treatment for head and neck squamous cell carcinoma (HNSCC) can lead to considerable functional impairment. As a result, HNSCC patients experience significant decrements in quality of life, high ...levels of emotional distress, deteriorations in interpersonal relations, and increased social isolation. Studies suggest that HNSCC patients may have extensive informational and psychosocial needs that are not being adequately addressed. However, few programs have been developed to address the needs of HNSCC patients. Therefore, we conducted a pilot study of HNSCC patients to: 1) characterize patients’ informational needs; and 2) describe preferred formats and time points for receiving such information. The majority of participants desired additional information regarding treatment options, managing changes in swallowing and speaking, and staying healthy after treatment. Overall, patients with early-stage disease reported more informational needs compared to patients with advanced disease. Female patients were more likely to desire information about coping with emotional stress and anxiety than male patients. Younger patients (29–49 years) were more interested in receiving information about sexuality after cancer compared to their older (50+) counterparts. Although information was requested throughout the cancer trajectory, most patients preferred to receive such information at diagnosis or within 1–3 months post-treatment. The majority of patients reported having computer and Internet access, and they were most receptive to receiving information delivered via the Internet, from a DVD, or from pamphlets and booklets. The relatively high percentage of patients with computer and Internet access reflects a growing trend in the United States and supports the feasibility of disseminating health information to this patient population via Internet-based programs.
The utility of breast magnetic resonance imaging in patients receiving neoadjuvant chemotherapy is not well defined. We compared serial magnetic resonance imaging examinations with histologic ...posttreatment examinations in patients treated with primary chemotherapy for locally advanced breast cancer.
Eligible patients with locally advanced breast cancer received doxorubicin 60 mg/m(2) and docetaxel 60 mg/m(2) (with granulocyte colony stimulating factor support) every 14 days for a maximum of six cycles. Breast magnetic resonance imaging was performed at baseline and repeated every two cycles. Surgery (either local excision or mastectomy) was performed after six cycles in responding or stable patients. Residual tumor size on pathology and preoperative magnetic resonance imaging was compared; concordance was defined as a < or = 0.5-cm difference.
To date, three of 17 enrolled subjects (17.6%) attained pathologic complete response, and three additional patients attained near pathologic complete response, with residual foci of < or = 1 mm. Of these six patients, only one was disease-free by magnetic resonance imaging. Discordance between magnetic resonance imaging findings and pathologic evaluation was found in four of six patients (66.6%) who obtained pathologic complete response or near pathologic complete response. In the three patients in whom four axillary lesions were followed with magnetic resonance imaging, discordance was found in all four lesions, with magnetic resonance imaging overestimating pathologic disease in all cases.
Our findings caution that magnetic resonance imaging may frequently overestimate residual invasive carcinoma after neoadjuvant chemotherapy. These results contradict previous studies suggesting that postchemotherapy magnetic resonance imaging may underestimate residual cancer. The use of magnetic resonance imaging in evaluating response to therapy in locally advanced breast cancer should be further studied.
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