-
The New England Journal of Medicine Jul 2023Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain.
METHODS
We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects.
RESULTS
From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy.
CONCLUSIONS
In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).
Topics: Adult; Humans; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Fluorouracil; Leucovorin; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Organ Sparing Treatments; Oxaliplatin; Rectal Neoplasms; Preoperative Care; Preoperative Period
PubMed: 37272534
DOI: 10.1056/NEJMoa2303269 -
Viruses Jun 2023Human papillomavirus (HPV) is causally associated with 5% of cancers, including cancers of the cervix, penis, vulva, vagina, anus and oropharynx. The most carcinogenic... (Review)
Review
Human papillomavirus (HPV) is causally associated with 5% of cancers, including cancers of the cervix, penis, vulva, vagina, anus and oropharynx. The most carcinogenic HPV is HPV-16, which dominates the types causing cancer. There is also sufficient evidence that HPV types 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 cause cervical cancer. The L1 protein, which, when assembled into virus-like particles, induces HPV-type-specific neutralising antibodies, forms the basis of all commercial HPV vaccines. There are six licensed prophylactic HPV vaccines: three bivalent, two quadrivalent and one nonavalent vaccine. The bivalent vaccines protect from HPV types 16 and 18, which are associated with more than 70% of cervical cancers. Prophylactic vaccination targets children before sexual debut, but there are now catch-up campaigns, which have also been shown to be beneficial in reducing HPV infection and disease. HPV vaccination of adults after treatment for cervical lesions or recurrent respiratory papillomatosis has impacted recurrence. Gender-neutral vaccination will improve herd immunity and prevent infection in men and women. HPV vaccines are immunogenic in people living with HIV, but more research is needed on the long-term impact of vaccination and to determine whether further boosters are required.
Topics: Adult; Male; Child; Humans; Female; Human Papillomavirus Viruses; Papillomavirus Infections; Vaccinology; Uterine Cervical Neoplasms; Papillomavirus Vaccines; Human papillomavirus 16; Vaccines, Combined
PubMed: 37515128
DOI: 10.3390/v15071440 -
Abdominal Radiology (New York) Sep 2023The Society of Abdominal Radiology's Colorectal and Anal Cancer Disease-Focused Panel (DFP) first published a rectal cancer lexicon paper in 2019. Since that time, the... (Review)
Review
The Society of Abdominal Radiology's Colorectal and Anal Cancer Disease-Focused Panel (DFP) first published a rectal cancer lexicon paper in 2019. Since that time, the DFP has published revised initial staging and restaging reporting templates, and a new SAR user guide to accompany the rectal MRI synoptic report (primary staging). This lexicon update summarizes interval developments, while conforming to the original lexicon 2019 format. Emphasis is placed on primary staging, treatment response, anatomic terminology, nodal staging, and the utility of specific sequences in the MRI protocol. A discussion of primary tumor staging reviews updates on tumor morphology and its clinical significance, T1 and T3 subclassifications and their clinical implications, T4a and T4b imaging findings/definitions, terminology updates on the use of MRF over CRM, and the conundrum of the external sphincter. A parallel section on treatment response reviews the clinical significance of near-complete response and introduces the lexicon of "regrowth" versus "recurrence". A review of relevant anatomy incorporates updated definitions and expert consensus of anatomic landmarks, including the NCCN's new definition of rectal upper margin and sigmoid take-off. A detailed review of nodal staging is also included, with attention to tumor location relative to the dentate line and locoregional lymph node designation, a new suggested size threshold for lateral lymph nodes and their indications for use, and imaging criteria used to differentiate tumor deposits from lymph nodes. Finally, new treatment terminologies such as organ preservation, TNT, TAMIS and watch-and-wait management are introduced. This 2023 version aims to serve as a concise set of up-to-date recommendations for radiologists, and discusses terminology, classification systems, MRI and clinical staging, and the evolving concepts in diagnosis and treatment of rectal cancer.
Topics: Humans; Rectal Neoplasms; Anus Neoplasms; Rectum; Neoplasm Staging; Magnetic Resonance Imaging; Radiology
PubMed: 37145311
DOI: 10.1007/s00261-023-03893-2 -
American Journal of Obstetrics and... Mar 2024Perineal trauma after vaginal birth is common, with approximately 9 of 10 women being affected. Second-degree perineal tears are twice as likely to occur in primiparous... (Review)
Review
Perineal trauma after vaginal birth is common, with approximately 9 of 10 women being affected. Second-degree perineal tears are twice as likely to occur in primiparous births, with a incidence of 40%. The incidence of obstetrical anal sphincter injury is approximately 3%, with a significantly higher rate in primiparous than in multiparous women (6% vs 2%). Obstetrical anal sphincter injury is a significant risk factor for the development of anal incontinence, with approximately 10% of women developing symptoms within a year following vaginal birth. Obstetrical anal sphincter injuries have significant medicolegal implications and contribute greatly to healthcare costs. For example, in 2013 and 2014, the economic burden of obstetrical anal sphincter injuries in the United Kingdom ranged between £3.7 million (with assisted vaginal birth) and £9.8 million (with spontaneous vaginal birth). In the United States, complications associated with trauma to the perineum incurred costs of approximately $83 million between 2007 and 2011. It is therefore crucial to focus on improvements in clinical care to reduce this risk and minimize the development of perineal trauma, particularly obstetrical anal sphincter injuries. Identification of risk factors allows modification of obstetrical practice with the aim of reducing the rate of perineal trauma and its attendant associated morbidity. Risk factors associated with second-degree perineal trauma include increased fetal birthweight, operative vaginal birth, prolonged second stage of labor, maternal birth position, and advanced maternal age. With obstetrical anal sphincter injury, risk factors include induction of labor, augmentation of labor, epidural, increased fetal birthweight, fetal malposition (occiput posterior), midline episiotomy, operative vaginal birth, Asian ethnicity, and primiparity. Obstetrical practice can be modified both antenatally and intrapartum. The evidence suggests that in the antenatal period, perineal massage can be commenced in the third trimester of pregnancy to increase muscle elasticity and allow stretching of the perineum during birth, thereby reducing the risk of tearing or need for episiotomy. With regard to the intrapartum period, there is a growing body of evidence from the United Kingdom, Norway, and Denmark suggesting that the implementation of quality improvement initiatives including the training of clinicians in manual perineal protection and mediolateral episiotomy can reduce the incidence of obstetrical anal sphincter injury. With episiotomy, the International Federation of Gynecology and Obstetrics recommends restrictive rather than routine use of episiotomy. This is particularly the case with unassisted vaginal births. However, there is a role for episiotomy, specifically mediolateral or lateral, with assisted vaginal births. This is specifically the case with nulliparous vacuum and forceps births, given that the use of mediolateral or lateral episiotomy has been shown to significantly reduce the incidence of obstetrical anal sphincter injury in these groups by 43% and 68%, respectively. However, the complications associated with episiotomy including perineal pain, dyspareunia, and sexual dysfunction should be acknowledged. Despite considerable research, interventions for reducing the risk of perineal trauma remain a subject of controversy. In this review article, we present the available data on the prevention of perineal trauma by describing the risk factors associated with perineal trauma and interventions that can be implemented to prevent perineal trauma, in particular obstetrical anal sphincter injury.
Topics: Pregnancy; Female; Humans; Birth Weight; Episiotomy; Parity; Parturition; Lacerations; Anal Canal; Risk Factors; Perineum; Obstetric Labor Complications
PubMed: 37635056
DOI: 10.1016/j.ajog.2022.06.021