Systemic and tumor-directed therapy for oligometastatic prostate cancer: study protocol for a phase II trial for veterans with de novo oligometastatic disease.

BACKGROUND: The treatment paradigm for metastatic hormone-sensitive prostate cancer (mHSPC) patients is evolving. PET/CT now offers improved sensitivity and accuracy in staging. Recent randomized trial data supports escalated hormone therapy, local primary tumor therapy, and metastasis-directed therapy. The impact of combining such therapies into a multimodal approach is unknown. This Phase II single-arm clinical trial sponsored and funded by Veterans Affairs combines local, metastasis-directed, and systemic therapies to durably render patients free of detectable disease off active therapy. METHODS: Patients with newly-diagnosed M1a/b prostate cancer (PSMA PET/CT staging is permitted) and 1-5 radiographically visible metastases (excluding pelvic lymph nodes) are undergoing local treatment with radical prostatectomy, limited duration systemic therapy for a total of six months (leuprolide, abiraterone acetate with prednisone, and apalutamide), metastasis-directed stereotactic body radiotherapy (SBRT), and post-operative fractionated radiotherapy if pT ≥ 3a, N1, or positive margins are present. The primary endpoint is the percent of patients achieving a serum PSA of < 0.05 ng/mL six months after recovery of serum testosterone ≥150 ng/dL. Secondary endpoints include time to biochemical progression, time to radiographic progression, time to initiation of alternative antineoplastic therapy, prostate cancer specific survival, health related quality-of-life, safety and tolerability. DISCUSSION: To our knowledge, this is the first trial that tests a comprehensive systemic and tumor directed therapeutic strategy for patients with newly diagnosed oligometastatic prostate cancer. This trial, and others like it, represent the critical first step towards curative intent therapy for a patient population where palliation has been the norm. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03298087 (registration date: September 29, 2017).

Near-complete pathological response with preoperative chemotherapy in a patient with metaplastic breast carcinoma.

Metaplastic breast carcinoma (MBC) is a rare form of breast cancer comprising less than 1% of all invasive breast carcinomas. There are no clinical studies available for the management of this rare disease and MBC is associated with a poor prognosis. We present a case of a 50-year-old female patient with MBC who showed a favorable response with preoperative chemotherapy. The patient presented with a palpable left breast mass, and diagnostic breast imaging showed a 4.4 cm mass in the left breast, which was biopsied. Pathological review led to a diagnosis of MBC. Staging workup for distant metastasis was negative. She received four cycles of dose-dense AC (doxorubicin and cyclophosphamide), followed by 10 weekly doses of carboplatin (area under the curve=2) and paclitaxel (80 mg/m). The patient underwent partial mastectomy and sentinel lymph node sampling, and pathological review indicated a near-complete pathological response, with few scattered malignant cells at the tumor bed. A current review of the literature on MBC is summarized in this report.

Complete pathologic response with combination oxaliplatin and 5-fluorouracil chemotherapy in an older patient with advanced gastric cancer.

Management of gastric cancer in older adults is challenging. Perioperative treatment with epirubicin, cisplatin, and 5-fluorouracil combination chemotherapy and surgery is considered the standard treatment of locally advanced gastric adenocarcinoma. However, this chemotherapy regimen is not well tolerated in older adults. Here, we report a case of an older patient with locally advanced gastric cancer who was treated with modified FOLFOX-6 (oxaliplatin, leucovorin, and 5-fluorouracil) regimen and achieved a complete pathological response.

Quality measures for supportive cancer care: the Cancer Quality-ASSIST Project.

Patients and physicians often cite symptom control as one of their most important goals in cancer care. Despite this, a previous systematic review found few tools for evaluating the quality of supportive cancer management. We developed a comprehensive set of quality indicators for evaluating pain and nonpain symptom management as well as care planning needs in cancer patients. Based on the prevalence and quality-of-life data, clinician-researchers prioritized pain, psychosocial distress, dyspnea, nausea and vomiting, fatigue and anorexia, treatment-associated toxicities, and information and care planning for quality-indicator development. Using search terms and selection criteria, we identified English-language documents from Medline (1997-2007) and Internet-based searches. Based on this evidence, clinician-reviewers proposed process quality indicators. We then used the VA Health Services Research and Development (VA HSR & D) appropriateness methods to compile the ratings of a multidisciplinary, international expert panel of the validity and feasibility of each indicator. The panel judged 92 out of 133 (69%) proposed quality indicators valid and feasible (15 out of 23 pain, 5 out of 6 depression, 8 out of 11 dyspnea, 15 out of 19 nausea and vomiting, 13 out of 26 fatigue and anorexia, 23 out of 32 other treatment-associated toxicities, and 13 out of 16 information and care planning). Of the final indicators, 67 are potentially useful for inpatient and 81 for outpatient evaluation, and 26 address screening, 12 diagnostic evaluation, 20 management, and 21 follow-up. These quality indicators provide evidence-explicit tools for measuring processes critical to ensuring high-quality supportive cancer care. Research is needed to characterize adherence to recommended practices and to evaluate the use of these measures in quality improvement efforts.

Need for a new treatment strategy: leptomeningeal carcinomatosis from gastric cancer.

Leptomeningeal carcinomatosis (LMC) is an extremely rare manifestation of gastric cancer. The treatment options are very limited for LMC; despite standard treatment with intrathecal chemotherapy, the prognosis is grim and the median overall survival is 3-4 months. Here we report on a patient with LMC from metastatic gastric cancer who was treated with a novel approach of high-dose systemic irinotecan, comparable with the dose utilized in treating primary brain tumors such as gliomas. Our patient not only had an excellent tumor response to this novel approach, but also had a prolonged overall survival of 13 months, which is unusual for LMC from gastric cancer.

Evidence-based standards for cancer pain management.

High-quality management of cancer pain depends on evidence-based standards for screening, assessment, treatment, and follow-up for general cancer pain and specific pain syndromes. We developed a set of standards through an iterative process of structured literature review and development and refinement of topic areas and standards and subjected recommendations to rating by a multidisciplinary expert panel. Providers should routinely screen for the presence or absence and intensity of pain and should perform descriptive pain assessment for patients with a positive screen, including assessment for likely etiology and functional impairment. For treatment, providers should provide pain education, offer breakthrough opioids in patients receiving long-acting formulations, offer bowel regimens in patients receiving opioids chronically, and ensure continuity of opioid doses across health care settings. Providers should also follow up on patients after treatment for pain. For metastatic bone pain, providers should offer single-fraction radiotherapy as an option when offering radiation, unless there is a contraindication. When spinal cord compression is suspected, providers should treat with corticosteroids and evaluate with whole-spine magnetic resonance imaging scan or myelography as soon as possible but within 24 hours. Providers should initiate definitive treatment (radiotherapy or surgical decompression) within 24 hours for diagnosed cord compression and should follow up on patients after treatment. These standards provide an initial framework for high-quality evidence-based management of general cancer pain and pain syndromes.

Evidence-based recommendations for cancer fatigue, anorexia, depression, and dyspnea.

PURPOSE The experience of patients with cancer often involves symptoms of fatigue, anorexia, depression, and dyspnea. METHODS We developed a set of standards through an iterative process of structured literature review and development and refinement of topic areas and standards and subjected recommendations to rating by a multidisciplinary expert panel. Results For fatigue, providers should screen patients at the initial visit, for newly identified advanced cancer, and at chemotherapy visits; assess for depression and insomnia in newly identified fatigue; and follow up after treatment for fatigue or a secondary cause. For anorexia, providers should screen at the initial visit for cancer affecting the oropharynx or gastrointestinal tract or advanced cancer, evaluate for associated symptoms, treat underlying causes, provide nutritional counseling for patients undergoing treatment that may affect nutritional intake, and follow up patients given appetite stimulants. For depression, providers should screen newly diagnosed patients, those started on chemotherapy or radiotherapy, those with newly identified advanced disease, and those expressing a desire for hastened death; document a treatment plan in diagnosed patients; and follow up response after treatment. For general dyspnea, providers should evaluate for causes of new or worsening dyspnea, treat or symptomatically manage underlying causes, follow up to evaluate treatment effectiveness, and offer opioids in advanced cancer when other treatments are unsuccessful. For dyspnea and malignant pleural effusions, providers should offer thoracentesis, follow up after thoracentesis, and offer pleurodesis or a drainage procedure for patients with reaccumulation and dyspnea. CONCLUSION These standards provide a framework for evidence-based screening, assessment, treatment, and follow-up for cancer-associated symptoms.

Evidence-based recommendations for information and care planning in cancer care.

The practice of oncology is characterized by challenging communication tasks that make it difficult to ensure optimal physician-patient information sharing and care planning. Discussions of diagnosis, prognosis, and patient goals are essential processes that inform decisions. However, data suggest that there are deficiencies in this area. We conducted a systematic review to identify the evidence supporting high-quality clinical practices for information and care planning in the context of cancer care as part of the RAND Cancer Quality-Assessing Symptoms, Side Effects, and Indicators of Supportive Treatment Project. Domains of information and care planning that are important for high-quality cancer care include integration of palliation into cancer care, advance care planning, sentinel events as markers for the need to readdress a patient's goals of care, and continuity of care planning. The standards presented here for information and care planning in cancer care should be incorporated into care pathways and should become the expectation rather than the exception.

Evidence-based recommendations for cancer nausea and vomiting.

The experience of patients living with cancer and being treated with chemotherapy often includes the symptoms of nausea and vomiting. To provide a framework for high-quality management of these symptoms, we developed a set of key targeted evidence-based standards through an iterative process of targeted systematic review, development, and refinement of topic areas and standards and consensus ratings by a multidisciplinary expert panel as part of the RAND Cancer Quality-Assessing Symptoms Side Effects and Indicators of Supportive Treatment Project. For nausea and vomiting, key clinical standards included screening at the initial outpatient and inpatient visit, prophylaxis for acute and delayed emesis in patients receiving moderate to highly emetic chemotherapy, and follow-up after treatment for nausea and vomiting symptoms. In addition, patients with cancer and small bowel obstruction were examined as a special subset of patients who present with nausea and vomiting. The standards presented here for preventing and managing nausea and vomiting in cancer care should be incorporated into care pathways and should become the expectation rather than the exception.