Eric O. Aboagye BPharm, MSc, PhD, Tara D. Barwick MBChB, MSc, Uwe Haberkorn MD
{"title":"Radiotheranostics in oncology: Making precision medicine possible","authors":"Eric O. Aboagye BPharm, MSc, PhD, Tara D. Barwick MBChB, MSc, Uwe Haberkorn MD","doi":"10.3322/caac.21768","DOIUrl":"https://doi.org/10.3322/caac.21768","url":null,"abstract":"<p>A quintessential setting for precision medicine, <i>theranostics</i> refers to a rapidly evolving field of medicine in which disease is diagnosed followed by treatment of disease-positive patients using tools for the therapy identical or similar to those used for the diagnosis. Against the backdrop of <i>only-treat-when-visualized</i>, the goal is a high therapeutic index with efficacy markedly surpassing toxicity. Oncology leads the way in theranostics innovation, where the approach has become possible with the identification of unique proteins and other factors selectively expressed in cancer versus healthy tissue, advances in imaging technology able to report these tissue factors, and major understanding of targeting chemicals and nanodevices together with methods to attach <i>labels or warheads</i> for imaging and therapy. <i>Radiotheranostics</i>—using radiopharmaceuticals—is becoming routine in patients with prostate cancer and neuroendocrine tumors who express the proteins PSMA (prostate-specific membrane antigen) and SSTR2 (somatostatin receptor 2), respectively, on their cancer. The palpable excitement in the field stems from the finding that a proportion of patients with large metastatic burden show complete and partial responses, and this outcome is catalyzing the search for more radiotheranostics approaches. Not every patient will benefit from radiotheranostics; but, for those who cross the <i>target-detected</i> line, the likelihood of response is very high.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"73 3","pages":"255-274"},"PeriodicalIF":254.7,"publicationDate":"2023-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21768","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6153607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cancer epigenetics in clinical practice","authors":"Veronica Davalos PhD, Manel Esteller MD, PhD","doi":"10.3322/caac.21765","DOIUrl":"https://doi.org/10.3322/caac.21765","url":null,"abstract":"<p>Cancer development is driven by the accumulation of alterations affecting the structure and function of the genome. Whereas genetic changes disrupt the DNA sequence, epigenetic alterations contribute to the acquisition of hallmark tumor capabilities by regulating gene expression programs that promote tumorigenesis. Shifts in DNA methylation and histone mark patterns, the two main epigenetic modifications, orchestrate tumor progression and metastasis. These cancer-specific events have been exploited as useful tools for diagnosis, monitoring, and treatment choice to aid clinical decision making. Moreover, the reversibility of epigenetic modifications, in contrast to the irreversibility of genetic changes, has made the epigenetic machinery an attractive target for drug development. This review summarizes the most advanced applications of epigenetic biomarkers and epigenetic drugs in the clinical setting, highlighting commercially available DNA methylation-based assays and epigenetic drugs already approved by the US Food and Drug Administration.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"73 4","pages":"376-424"},"PeriodicalIF":254.7,"publicationDate":"2022-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21765","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6234019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Ashley PhD, Claire Surr PhD, Rachael Kelley RMN, PhD, Mollie Price PhD, Alys Wyn Griffiths PhD, Nicole R. Fowler MHSA, PhD, Dana E. Giza MD, Richard D. Neal MBChB, FRCGP, PhD, Charlene Martin PhD, Jane B. Hopkinson RGN, PhD, Anita O’Donovan PhD, William Dale MD, PhD, Bogda Koczwara BMBS, MBioethics, Katie Spencer MB BChir, FRCR, PhD, Lynda Wyld MBChB, FRCS, PhD
{"title":"Cancer care for people with dementia: Literature overview and recommendations for practice and research","authors":"Laura Ashley PhD, Claire Surr PhD, Rachael Kelley RMN, PhD, Mollie Price PhD, Alys Wyn Griffiths PhD, Nicole R. Fowler MHSA, PhD, Dana E. Giza MD, Richard D. Neal MBChB, FRCGP, PhD, Charlene Martin PhD, Jane B. Hopkinson RGN, PhD, Anita O’Donovan PhD, William Dale MD, PhD, Bogda Koczwara BMBS, MBioethics, Katie Spencer MB BChir, FRCR, PhD, Lynda Wyld MBChB, FRCS, PhD","doi":"10.3322/caac.21767","DOIUrl":"https://doi.org/10.3322/caac.21767","url":null,"abstract":"<p>As many countries experience population aging, patients with cancer are becoming older and have more preexisting comorbidities, which include prevalent, age-related, chronic conditions such as dementia. <i>People living with dementia</i> (PLWD) are vulnerable to health disparities, and dementia has high potential to complicate and adversely affect care and outcomes across the cancer trajectory. This report offers an overview of dementia and its prevalence among patients with cancer and a summary of the research literature examining cancer care for PLWD. The reviewed research indicates that PLWD are more likely to have cancer diagnosed at an advanced stage, receive no or less extensive cancer treatment, and have poorer survival after a cancer diagnosis. These cancer disparities do not necessarily signify inappropriately later diagnosis or lower treatment of people with dementia as a group, and they are arguably less feasible and appropriate targets for care optimization. The reviewed research indicates that PLWD also have an increased risk of cancer-related emergency presentations, lower quality processes of cancer-related decision making, accessibility-related barriers to cancer investigations and treatment, higher <i>experienced</i> treatment burden and higher caregiver burden for families, and undertreated cancer-related pain. The authors propose that optimal cancer care for PLWD should focus on proactively minimizing these risk areas and thus must be highly person-centered, with holistic decision making, individualized reasonable adjustments to practice, and strong inclusion and support of family carers. Comprehensive recommendations are made for clinical practice and future research to help clinicians and providers deliver best and equitable cancer care for PLWD and their families.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"73 3","pages":"320-338"},"PeriodicalIF":254.7,"publicationDate":"2022-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21767","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6234015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vaibhav Wadhwa MD, Nicole Patel MD-DR, MBA, Dheera Grover MD, Faisal S. Ali MD, Nirav Thosani MD MHA
{"title":"Interventional gastroenterology in oncology","authors":"Vaibhav Wadhwa MD, Nicole Patel MD-DR, MBA, Dheera Grover MD, Faisal S. Ali MD, Nirav Thosani MD MHA","doi":"10.3322/caac.21766","DOIUrl":"https://doi.org/10.3322/caac.21766","url":null,"abstract":"<p>Cancer is one of the foremost health problems worldwide and is among the leading causes of death in the United States. Gastrointestinal tract cancers account for almost one third of the cancer-related mortality globally, making it one of the deadliest groups of cancers. Early diagnosis and prompt management are key to preventing cancer-related morbidity and mortality. With advancements in technology and endoscopic techniques, endoscopy has become the core in diagnosis and management of gastrointestinal tract cancers. In this extensive review, the authors discuss the role endoscopy plays in early detection, diagnosis, and management of esophageal, gastric, colorectal, pancreatic, ampullary, biliary tract, and small intestinal cancers.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"73 3","pages":"286-319"},"PeriodicalIF":254.7,"publicationDate":"2022-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21766","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6182221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ilana Cass MD, Jill N. T. Roberts MD, Philip R. Benoit, Nicholas V. Jensen
{"title":"Multidisciplinary considerations in the maintenance treatment of poly(ADP-ribose) polymerase inhibitors for homologous recombination-proficient, advanced-stage epithelial ovarian cancer","authors":"Ilana Cass MD, Jill N. T. Roberts MD, Philip R. Benoit, Nicholas V. Jensen","doi":"10.3322/caac.21764","DOIUrl":"https://doi.org/10.3322/caac.21764","url":null,"abstract":"<p>A 73-year-old, para five, postmenopausal woman with a history of type 2 diabetes mellitus, hypertension, hyperlipidemia, sarcoidosis, and osteoarthritis presented to the Emergency Department with shortness of breath, abdominal distention, and early satiety for 1 month. She had a remote history of an abdominal hysterectomy for uterine fibroids. Chest x-ray and subsequent computed tomography (CT) of the chest revealed a moderate, right-sided pleural effusion with compressive atelectasis. A CT of the abdomen and pelvis revealed a large, complex, cystic, and solid left adnexal mass measuring 8 × 13 cm with a smaller mass in the right lower pelvis measuring 4.3 cm. Omental thickening and ascites also were noted. The patient was admitted to the hospital and underwent an ultrasound-guided thoracentesis. One liter of fluid was drained and sent for cytology, which returned positive for malignancy. Her cancer antigen 125 level was elevated at 424 U/ml. The patient was discharged home with a plan for outpatient gynecologic oncology follow-up given the concern for ovarian cancer.</p><p>The patient was seen in consultation and an extensive history was taken. She denied a family history of cancer. Management options were discussed, including either primary cytoreductive surgery followed by chemotherapy or neoadjuvant chemotherapy with possible interval cytoreduction. Given the extent of her disease on imaging and her presentation, with symptomatic pleural effusions limiting her mobility and functional status, it was recommended she undergo neoadjuvant chemotherapy. While awaiting chemotherapy, the patient was readmitted to an outside hospital with recurrent shortness of breath caused by the re-accumulation of pleural fluid. She underwent repeat thoracentesis, and a PleurX catheter (Becton, Dickinson and Company) was placed. An omental biopsy was also performed and revealed metastatic adenocarcinoma of Mullerian origin.</p><p>The patient subsequently completed four cycles of neoadjuvant chemotherapy with paclitaxel, carboplatin, and bevacizumab, with normalization of her cancer antigen 125 level to 18 U/ml after three cycles. She developed worsening peripheral neuropathy grade 2 between cycles three and four despite the use of B6, glutamine, and alpha lipoic acid. Preoperative CT demonstrated an interval decrease in size of her bilateral adnexal masses and resolution of her omental caking, ascites, and pleural effusion. Her PleurX catheter was removed before surgery. At the time of exploratory laparotomy, she had a palpably thickened omentum and normal adnexa. She underwent bilateral salpingo-oophorectomy, infracolic omentectomy, biopsies, and external iliac lymph node sampling, with no gross residual cancer palpated or visualized at the end of the case (R0 resection). Pathology revealed microscopic, high-grade, serous epithelial ovarian adenocarcinoma involving the ovaries and omentum.</p><p>The patient's postoperative course was complicated by readmission ","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"73 1","pages":"8-16"},"PeriodicalIF":254.7,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6209597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tyler B. Kratzer MPH, Ahmedin Jemal DVM, PhD, Kimberly D. Miller MPH, Sarah Nash PhD, Charles Wiggins PhD, Diana Redwood PhD, Robert Smith PhD, Rebecca L. Siegel MPH
{"title":"Cancer statistics for American Indian and Alaska Native individuals, 2022: Including increasing disparities in early onset colorectal cancer","authors":"Tyler B. Kratzer MPH, Ahmedin Jemal DVM, PhD, Kimberly D. Miller MPH, Sarah Nash PhD, Charles Wiggins PhD, Diana Redwood PhD, Robert Smith PhD, Rebecca L. Siegel MPH","doi":"10.3322/caac.21757","DOIUrl":"https://doi.org/10.3322/caac.21757","url":null,"abstract":"<p>American Indian and Alaska Native (AIAN) individuals are diverse culturally and geographically but share a high prevalence of chronic illness, largely because of obstacles to high-quality health care. The authors comprehensively examined cancer incidence and mortality among non-Hispanic AIAN individuals, compared with non-Hispanic White individuals for context, using population-based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Overall cancer rates among AIAN individuals were 2% higher than among White individuals for incidence (2014 through 2018, confined to Purchased/Referred Care Delivery Area counties to reduce racial misclassification) but 18% higher for mortality (2015 through 2019). However, disparities varied widely by cancer type and geographic region. For example, breast and prostate cancer mortality rates are 8% and 31% higher, respectively, in AIAN individuals than in White individuals despite lower incidence and the availability of early detection tests for these cancers. The burden among AIAN individuals is highest for infection-related cancers (liver, stomach, and cervix), for kidney cancer, and for colorectal cancer among indigenous Alaskans (91.3 vs. 35.5 cases per 100,000 for White Alaskans), who have the highest rates in the world. Steep increases for early onset colorectal cancer, from 18.8 cases per 100,000 Native Alaskans aged 20–49 years during 1998 through 2002 to 34.8 cases per 100,000 during 2014 through 2018, exacerbated this disparity. Death rates for infection-related cancers (liver, stomach, and cervix), as well as kidney cancer, were approximately two-fold higher among AIAN individuals compared with White individuals. These findings highlight the need for more effective strategies to reduce the prevalence of chronic oncogenic infections and improve access to high-quality cancer screening and treatment for AIAN individuals. Mitigating the disparate burden will require expanded financial support of tribal health care as well as increased collaboration and engagement with this marginalized population.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"73 2","pages":"120-146"},"PeriodicalIF":254.7,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21757","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6156251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Colonoscopies for patients aged 45–49 years yield positive results","authors":"Mike Fillon","doi":"10.3322/caac.21762","DOIUrl":"https://doi.org/10.3322/caac.21762","url":null,"abstract":"<p>In response to the increase in colon cancer rates in younger individuals in 2018, the ACS—with other organizations following suit—recommended lowering the age for starting colorectal cancer screening of average-risk individuals to 45 years. Researchers from the Stanford University School of Medicine in California believe that enough time has now passed to begin assessing the impact of this change. Specifically, they wanted to examine any changes in the proportion of younger people screened in Stanford endoscopy clinics and whether the inclusion of the younger subjects would dilute the ADR. The study appears in <i>Clinical Gastroenterology and Hepatology</i> (doi:10.1016/j.cgh.2022.04.037.)</p><p>The researchers used data from Stanford’s Colonoscopy Quality Assurance Program, which collects information from four of the university’s Northern California endoscopy clinics. The researchers compared subjects who underwent screening colonoscopy during two periods. Period 1 covers October 2017 through December 2018 and represents the time before the 2018 ACS guideline. Period 2 covers January 2019 through August 2021, after dissemination of the new guideline. Subjects from each time period were divided into several groups: patients between the ages of 45 and 49 years and those 50 years old or older (in five-year age groups) at their initial colonoscopies as well as patients in the same age groups who were undergoing rescreening colonoscopy.</p><p>For each group and by time period, the researchers compared detection rates for adenomas, advanced adenomas, sessile serrated lesions (SSLs), and advanced SSLs; the mean number of adenomas per colonoscopy; and the mean number of lesions per colonoscopy.</p><p>Dr Ladabaum, who is the lead author of the study, and his colleagues compared detection rates from Period 2 to Period 1 for patients aged 45–50 years to explore whether patients at low risk for colorectal neoplasia might be self-selecting for screening in Period 2. “When the ACS guidelines were first published, concerns were raised that the 45- to 49-yearolds who would present for screening might be health-conscious persons with the best access to medical services, and that these persons might in fact be a low-risk group.”</p><p>The researchers also compared Period 2 detection rates among the younger patients with those of the older groups (those who underwent initial screening or rescreening) for whom colorectal cancer screening is encouraged under new and previous guidelines.</p><p>From records of 29,166 unique colonoscopies, the study selected patients who had undergone colonoscopy with documentation of the extent of examination to the cecum and a Boston Bowel Preparation Score of at least 2 in each segment (indicating bowel preparation that was adequate for visualizing the bowel lining). The final study data set included 7990 patients who had undergone colonoscopies from October 2017 through August 2021; 4266 were first-time colonoscopies, and 3724 w","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"72 6","pages":"507-509"},"PeriodicalIF":254.7,"publicationDate":"2022-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21762","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6139213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sustained weight loss may reduce cancer risk","authors":"Mike Fillon","doi":"10.3322/caac.21761","DOIUrl":"https://doi.org/10.3322/caac.21761","url":null,"abstract":"<p>Although it is widely accepted that obesity is a cancer risk factor, there has been little research showing that losing weight and maintaining that loss reduce the risk of developing and possibly dying of certain cancers. A new study by Cleveland Clinic Health System (CCHS) researchers, published in the Journal of the American Medical Association (doi:10.1001/jama.2022.9009), does just that by focusing on patients who underwent bariatric surgery.</p><p>Although the biological mechanisms are still incompletely understood, it is believed by many that obesity can affect cancer development and growth by causing increased inflammation, by altering microbiota, by causing insulin resistance, and by increasing the levels of circulating insulin-like growth factor, estrogens, and adipokines.</p><p>Lead study author Ali Aminian, MD, professor of surgery at the Lerner College of Medicine and director of Cleveland Clinic’s Bariatric & Metabolic Institute, says that the researchers focused on bariatric surgery because it is an effective and long-lasting way for patients with obesity to lose weight.</p><p>The primary composite end point of this retrospective, observational, matched cohort study was the time to first incidence of one of 13 obesity-associated cancers: esophageal adenocarcinoma; renal cell carcinoma; postmenopausal breast cancer; cancer of the gastric cardia, colon, rectum, liver, gallbladder, pancreas, ovary, corpus uteri, or thyroid; and multiple myeloma. The secondary end point was cancer-related mortality.</p><p>The SPLENDID study included 5053 adult patients with obesity who underwent either Roux-en-Y gastric bypass or sleeve gastrectomy at Cleveland Clinic hospitals between 2004 and 2017. Each surgical patient was matched with five patients who did not undergo bariatric surgery. These 25,265 nonsurgical control patients were selected via a logistic regression model based on 10 potential self-reported potential confounders, including the following: race (Black, White, or other), body mass index (35–39.9, 40–44.9, 45–49.9, 50–54.9, 55–59.9, or 60–80 kg/m<sup>2</sup>), smoking history (never, former, or current), presence of type 2 diabetes, Elixhauser Comorbidity Index, Charlson Comorbidity Index, and state of residence (classified as Florida or as Ohio [because many patients were treated at CCHS facilities in those states] or as other US states combined). The median age of the patients was 46 years. Most were female (77%), and 73% were White. The median follow-up interval was 5.8 years for the bariatric surgery group and 6.1 years for patients in the nonsurgical control group.</p><p>The CCHS researchers found rather dramatic results: The bariatric surgery patients had a 32% lower incidence of obesity-associated cancer and a 48% lower risk of death from cancer than the patients in the nonsurgical control group.</p><p>At the 10-year mark, the bariatric surgery group lost 19.2% more body weight than the control group did; this corresponde","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"72 6","pages":"505-506"},"PeriodicalIF":254.7,"publicationDate":"2022-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21761","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6139212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jung Julie Kang MD, PhD, Yao Yu MD, Linda Chen MD, Kaveh Zakeri MD, Daphna Yael Gelblum MD, Sean Matthew McBride MD, MPH, Nadeem Riaz MD, C. Jillian Tsai MD, PhD, Anuja Kriplani MD, Tony K. W. Hung MD, James V. Fetten MD, Lara A. Dunn MD, Alan L. Ho MD, Jay O. Boyle MD, Ian S. Ganly MD, PhD, Bhuvanesh Singh MD, PhD, Eric J. Sherman MD, David G. Pfister MD, Richard J. Wong MD, Nancy Y. Lee MD
{"title":"Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus-associated oropharyngeal cancer","authors":"Jung Julie Kang MD, PhD, Yao Yu MD, Linda Chen MD, Kaveh Zakeri MD, Daphna Yael Gelblum MD, Sean Matthew McBride MD, MPH, Nadeem Riaz MD, C. Jillian Tsai MD, PhD, Anuja Kriplani MD, Tony K. W. Hung MD, James V. Fetten MD, Lara A. Dunn MD, Alan L. Ho MD, Jay O. Boyle MD, Ian S. Ganly MD, PhD, Bhuvanesh Singh MD, PhD, Eric J. Sherman MD, David G. Pfister MD, Richard J. Wong MD, Nancy Y. Lee MD","doi":"10.3322/caac.21758","DOIUrl":"https://doi.org/10.3322/caac.21758","url":null,"abstract":"<p>The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long-term morbidities with chemoradiation and the favorable prognosis of HPV-positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head-and-neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de-escalation. National database studies estimate that up to one third of patients receive nonstandard de-escalated treatments, which have subspecialty-specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV-positive OPC de-escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de-escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy-based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"73 2","pages":"164-197"},"PeriodicalIF":254.7,"publicationDate":"2022-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5872026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dimitrios Moris MD, MSc, PhD, Manisha Palta MD, Charles Kim MD, Peter J. Allen MD, Michael A. Morse MD, Michael E. Lidsky MD
{"title":"Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians","authors":"Dimitrios Moris MD, MSc, PhD, Manisha Palta MD, Charles Kim MD, Peter J. Allen MD, Michael A. Morse MD, Michael E. Lidsky MD","doi":"10.3322/caac.21759","DOIUrl":"https://doi.org/10.3322/caac.21759","url":null,"abstract":"<p>Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in the majority of patients. Approximately 20%–30% of patients are eligible for resection, which is considered the only potentially curative treatment; and, after resection, a median survival of 53 months has been reported when sequenced with adjuvant capecitabine. For the 70%–80% of patients who present with locally unresectable or distant metastatic disease, systemic therapy may delay progression, but survival remains limited to approximately 1 year. For the past decade, doublet chemotherapy with gemcitabine and cisplatin has been considered the most effective first-line regimen, but results from the recent use of triplet regimens and even immunotherapy may shift the paradigm. More effective treatment strategies, including those that combine systemic therapy with locoregional therapies like radioembolization or hepatic artery infusion, have also been developed. Molecular therapies, including those that target fibroblast growth factor receptor and isocitrate dehydrogenase, have recently received US Food and Drug Administration approval for a defined role as second-line treatment for up to 40% of patients harboring these actionable genomic alterations, and whether they should be considered in the first-line setting is under investigation. Furthermore, as the oncology field seeks to expand indications for immunotherapy, recent data demonstrated that combining durvalumab with standard cytotoxic therapy improved survival in patients with ICC. This review focuses on the current and future strategies for ICC treatment, including a summary of the primary literature for each treatment modality and an algorithm that can be used to drive a personalized and multidisciplinary approach for patients with this challenging malignancy.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"73 2","pages":"198-222"},"PeriodicalIF":254.7,"publicationDate":"2022-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5936950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}