Breast journal 2020 special issue: Post-mastectomy radiation: Tracking changes in the standard of care over 25 years.

This is an invited review article, tracking the changes in the indications and use of post-mastectomy radiation over the last 25 years. While radiation after mastectomy has been in use for decades, several key prospective randomized trials published in recent years have changed and strengthened role of this modality. This manuscript will track the milestones over the last three decades.

The evolution of adjuvant radiation therapy for early-stage and locally advanced breast cancer.

Adjuvant radiation therapy is often delivered after breast cancer surgery, both in the post-lumpectomy and post-mastectomy settings. Standard fractionation whole breast irradiation (SF-WBI), which is typically delivered over 5-7 weeks, was previously considered the standard of care. More recent data has helped to establish hypofractionated whole breast irradiation (HF-WBI), which consists of a 3-4 week regimen, as a new standard of care. This article provides an overview of the major randomized trials that support the routine use of HF-WBI for the majority of patients undergoing breast-conserving surgery for early-stage breast cancer. Newer data on the use of a hypofractionated approach in the post-mastectomy setting, as well as ongoing randomized trials addressing this topic, are also discussed.

The evolution of regional nodal irradiation in breast cancer.

Breast cancer regional node management has witnessed many changes over the last decade. Advances in surgical techniques establishing sentinel lymph node biopsy as an alternative to axillary dissection, use of microarray technology for subtyping breast cancer to guide systemic therapy selection, and the expansion of the systemic therapy armamentarium including targeted agents have contributed to changing our strategy from one size fits all to a more tailored approach. There have also been recent landmark studies reported that significantly impact clinical practice in the regional nodal management of breast cancer. As the molecular era of personalized medicine is approaching, we hereby revisit the rational, benefit, and controversies of regional nodal irradiation in the light of the most recent publications.

Milestones in breast cancer treatment.

Modern treatment started in the 1880s with Halsted's mastectomy. The next milestone-a century later-was breast-conserving surgery, with equivalent survival but better esthetic outcomes than mastectomy. Sentinel node biopsy, introduced in the 1990s, was a milestone that permitted avoidance of axillary dissection if the sentinel node was disease-free. Chemotherapy was established for early breast cancer in the 1980s and its efficacy continues to improve; however side effects remain a concern, particularly since chemotherapy does not benefit most patients. External whole breast irradiation was introduced with conservative surgery, as it reduces recurrences. By the 2000s, 3-week regimens had been shown equivalent to standard 6-week regimens-easing pressure on patients and radiation centers. Intraoperative partial breast irradiation is potentially more beneficial as it permits complete local treatment in a single session; however, trials show that patients must be very carefully selected. From the 1990s irradiation technology was combined with imaging and computer technologies to produce equipment that directs radiation to more precisely defined target volumes, allowing increased dose to the target and markedly reduced dose to nearby tissues. Irradiation systems are evolving rapidly but are being implemented without data on long-term morbidity or efficacy, while costs rise steeply. The first targeted treatment was tamoxifen, a selective estrogen receptor inhibitor. Since its widespread use starting in the 1980s, tamoxifen has saved the lives or prolonged the survival of millions with estrogen-positive disease; it is cheap and has limited (but not negligible) side effects. The same cannot be said of newer targeted treatments like trastuzumab and pertuzumab, which, although effective against human epidermal growth factor receptor 2-positive cancer, come with important side effects and huge costs. Breast cancer mortality is declining in rich countries, but treatments have become more demanding and more expensive, so the outlook for the increasing numbers of women worldwide who develop the disease is uncertain.

Future directions from past experience: a century of prostate radiotherapy.

Prostate cancer is the most commonly diagnosed noncutaneous malignancy in men, yet 100 years ago it was considered a rare disease. Over the past century, radiation therapy has evolved from a radium source placed in the urethra to today's advanced proton therapy delivered by only a few specialized centers. As techniques in radiation have evolved, the treatment of localized prostate cancer has become one of the most debated topics in oncology. Today, patients with prostate cancer must often make a difficult decision between multiple treatment modalities, each with the risk of permanent sequelae, without robust randomized data to compare every treatment option. Meanwhile, opinions of urologists and radiation oncologists about the risks and benefits involved with each modality vary widely. Further complicating the issue is rapidly advancing technology which often outpaces clinical data. This article represents a complete description of the evolution of prostate cancer radiation therapy with the goal of illuminating the historical basis for current challenges facing oncologists and their patients.

A history of surgery for locally-advanced (T4) cancer of the thoracic esophagus in Japan and a personal perspective.

The history of esophageal surgery in Japan can be divided into three periods, an era of safety from 1930 to 1980, an era of radicality from 1980 to 2000, and the era of quality of life (QOL) from 2000 to the present. The treatment for T4 cancers of the thoracic esophagus has also changed over time from preoperative radiotherapy, combined resection of the neighboring organs with esophagectomy, and to definitive chemoradiotherapy (dCRT) with salvage surgery. At present, almost all patients with an unresectable T4 esophageal cancer receives dCRT. However, there are many patients with a residual or recurrent tumor after dCRT. Salvage surgery for such patients often results in incomplete resection of the tumor because the tumor involves the trachea and/or aorta. New techniques to enable the resection of such neighboring organs even during salvage surgery are needed. In the future, the mainstay of treatment for esophageal cancer will be CRT with the foreseeable progress in new drugs and new techniques of radiotherapy. Surgery will be indicated for a local failure after CRT, while combined resection of the neighboring organs will be necessary to treat a local failure after CRT for T4 cancers. New surgical techniques have to be developed through some application of new devices and equipment.

The lost art of localization: Franc Ingraham's legacy in pediatric neurosurgery.

The authors describe an 8-year-old girl who underwent emergency posterior fossa surgery for resection of a large cerebellar astrocytoma in November 1939. The surgery was carried out by Franc D. Ingraham at Boston Children's Hospital a decade after he established the first pediatric neurosurgical service in the world at the same institution. Four years later the tumor recurred and the patient underwent repeat resection followed by external-beam radiation therapy. The pathological diagnosis by Sidney Farber was fibrillary astrocytoma. The young girl is currently a healthy, functional 82-year-old woman. The authors believe that this 74-year follow-up represents one of the longest in history, if not the longest, of a patient undergoing resection of a brain tumor. A recent MRI study shows postoperative changes with no evidence of residual or recurrent tumor. The original block tissue specimen had been preserved. It was restained and examined, revealing the pathological diagnosis to be juvenile pilocytic astrocytoma. The case is analyzed in the context of Ingraham's powerful and lasting impact on the field of pediatric neurosurgery.

Treatment options in surgical management of breast cancer.

The surgical approach to primary operable breast cancer has changed greatly within the past millenium. In the last 20 years collaborative patient trials have generated a wealth of valuable information that now allows us the opportunity to offer women a number of surgical options where before there was only one. The long awaited results of the chemoprevention trials will almost certainly change our surgical approach even further. Many questions regarding the management of breast cancer remain unanswered.