Aroor R. Rao

Patterns of recurrence following curative resection alone for adenocarcinoma of the rectum and sigmoid colon.

Two‐hundred‐four patients with previously untreated adenocarcinoma of rectum, rectosigmoid, and sigmoid colon were retrospectively evaluated to determine patterns of recurrence following curative resection. Seventy‐eight (38%) subsequently developed recurrent disease. Of these, 40% (31/78) presented with local recurrence alone, 28% (22/78) with regional recurrence, 15% (12/78) with concomitant local recurrence and distant metastasis, and 17% (13/78) with distant metastasis alone. The degree of tumor anaplasia and depth of tumor penetration into the bowel wall influenced the rate of local recurrence. Through five years local recurrence without clinical evidence of distant metastasis was the most common cause of death. Need for adjuvant radiation therapy is discussed.

CHEMOTHERAPY AND LOW-DOSE RADIOTHERAPY IN THE TREATMENT OF HIV-INFECTED PATIENTS WITH CARCINOMA OF THE ANAL CANAL

PURPOSE To determine the efficacy and tolerance of a standardized protocol of chemotherapy and low-dose radiotherapy in the treatment of anal cancer in human immunodeficiency virus (HIV)-infected patients. METHODS AND MATERIALS Between 1987 and 1995, eight HIV-positive patients with squamous cell carcinoma of the anal canal, four of whom had acquired immunodeficiency syndrome (AIDS), received therapy at the Kaiser Permanente Medical Center. All patients were treated using a combined modality approach consisting of low-dose radiotherapy (30 Gy in 15 fractions delivered 5 days/week), and chemotherapy [1000 mg/m2 of 5-fluorouracil (5-FU) delivered on days 1-4 and 29-32 as a continuous infusion over 96 h, and 10 mg/m2 of mitomycin C delivered as a bolus injection on day 1]. Patients have been followed from 4 to 81 months (mean 41, median 38). RESULTS All eight patients completed the therapy with minor variations to the protocol, and all have attained a clinical complete response. Four patients are alive and free of disease, and four died as a result of complications of AIDS, but remained free of anal carcinoma. There were no mortalities from the protocol and the morbidity was acceptable. Only one patient each was noted to have Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Grade 4 hematologic and gastrointestinal acute toxicity, and no Grade 4 skin toxicity was noted. CONCLUSION This combined therapy is effective for HIV-infected patients and appears to be tolerable with acceptable toxicities. It is best applied to patients who are HIV positive, or who have AIDS without concurrent major opportunistic infections. This approach is reasonable and affords patients a reasonably good chance at sphincter preservation by avoiding abdominoperineal resection. The optimal therapy for HIV-positive patients with advanced AIDS remains less well defined.

Radiation tolerance of the vaginal mucosa.

Abstract Sixteen patients with cancer of the vagina that were controlled locally for a minimum of eighteen months after teletherapy (T) or brachytherapy (B) or both (T & B), were analyzed for radiation tolerance of the vaginal mucosa. The site of vaginal necrosis did not always coincide with the site of the tumor. The posterior wall appeared more vulnerable than the anterior or lateral walls. For the distal vaginal mucosa, necrosis requiring surgical intervention occurred following combined T & B, if summated rad exceeded 9800. The upper vagina tolerated higher dosages. No patient required surgery for upper vaginal necrosis even though summated (T & B) dosage up to 14,000 rad was applied. Placing radioactive needles on the surface of the vaginal cylinder with or without interstitial perinea) needles should be avoided. Further accumulation of data is needed to define these vaginal mucosa tolerance limits more closely.

Management of gastrointestinal lymphoma.

A STUDY WAS MADE OF 85 PATIENTS WITH PRIMARY gastrointestinal (GI) lymphoma. The occurrence was 40 (62%) in stomach, 15 (23%) in the small intestine, and 10 (15%) in colorectum. The majority of patients had their histology classified according to Rappaports classification. Diffuse histiocytic type had the worst prognosis (median survival 13.8 months), and nodular histology had the best prognosis. A modified staging system proposed by Black-ledge et al. was used. Patients who had their disease confined to one viscus (Stage I) or with spread to regional lymph nodes (Stage II) had an excellent prognosis, with a 5-year survival of 87 and 67%, respectively. However, those who had distant nodal involvement (Stage III, e.g., para-aortic nodes) or spread to adjacent organs within the abdomen (Stage IV) had worse prognosis, with 5-year survival of 40 and 13%, respectively. In Stage I, radiotherapy alone was as effective as surgical resection. None of the 11 patients treated by radiotherapy alone had perforation or bleeding. The 5-year disease-free survival was 51%.

A new staging system for irradiation injuries following treatment for cancer of the cervix uteri

Abstract Four hundred six patients have been reviewed following radiation therapy for carcinoma of the cervix. The classification of radiation injuries is variable from institution to institution. Some classify injuries as early and late; others, acute and chronic. The grading of injuries usually depends on organ orientation. This is not helpful since the morbidity depends on the extent of surgery needed to correct the injury. This paper consists of a report of the number of injuries in our series, related to the stage of cancer, radiation dosage, recurrences, performance status, and survival. A staging system for irradiation injuries is proposed which has been helpful to us in analyzing and documenting our injuries more precisely. In addition, an analysis is made of the response of 100 surviving patients to a questionnaire regarding the effect of the cancer and treatment on the personal life and relationships of the patient to family, husband, and friends.

Comparison of Toxicity and Treatment Outcomes in Hiv-positive Versus Hiv-negative Patients With Squamous Cell Carcinoma of the Anal Canal

Purpose: To compare the toxicity and treatment outcomes in human immunodeficiency virus (HIV)-positive versus HIV-negative patients with squamous cell carcinoma of the anal canal who underwent definitive concurrent chemoradiation at a single institution. Materials and Methods: Fifty-three consecutive HIV-positive patients treated between 1987 and 2013 were compared with 205 consecutive HIV-negative patients treated between 2003 and 2013. All patients received radiotherapy at a single regional facility. The median radiation dose was 54 Gy (range, 28 to 60 Gy). Concurrent chemotherapy consisted of 2 cycles 5-FU with mitomycin-C given on day 1±day 29). After treatment, patients were closely followed with imaging studies, clinical examinations, and rigid proctoscopies. Outcomes assessed were toxicity rates, progression-free survival, colostomy-free survival, cancer-specific survival, and overall survival. Results: Median follow-up was 34 months. Compared with HIV-negative patients, HIV-positive patients were younger (median age, 48 vs. 62 y) and predominantly male sex (98% of HIV-positive patients were male vs. 22% of HIV-negative patients). Of the HIV-positive patients, 37 (70%) were on highly active antiretroviral therapy, 26 (65%) had an undetectable viral load at the time of treatment, and 36 (72%) had a CD4 count>200 (mean CD4 count, 455). There were no significant differences in acute or late nonhematologic or hematologic toxicity rates between the 2 groups. At 3 years, there was no significant difference between HIV-positive and HIV-negative patients in regards to progression-free survival (75% vs. 76%), colostomy-free survival (85% vs. 85%), or cancer-specific survival (79% vs. 88%, P=0.36), respectively. On univariate analysis, there was a trend toward worse overall survival in HIV-positive patients (72% vs. 84% at 3 y, P=0.06). For the entire cohort, on multivariate analysis only male sex and stage were predictive of worse survival outcomes. HIV status was not associated with worse outcomes in Cox models. Conclusions: In the highly active antiretroviral therapy era, HIV-positive patients with anal cancer treated with standard definitive chemoradiation have equivalent toxicity and cancer-specific survival compared with HIV-negative patients.

Chemoradiotherapy for squamous cell carcinoma of the anal canal: Comparison of one versus two cycles mitomycin-C

BACKGROUND AND PURPOSE Concurrent chemoradiotherapy with 5-fluorouracil (5-FU) and mitomycin-C (MMC) is standard treatment for anal cancer. Randomized clinical trials in Europe have used 1 cycle MMC, while North American studies use 2 cycles. We compared treatment outcomes between patients treated with either 1 or 2 cycles of concurrent MMC. MATERIAL AND METHODS 217 consecutive patients were treated definitively with chemoradiation from 2004 to 2012 in an integrated health system. Concurrent chemotherapy regimen depended on individual practice, and consisted of 2 cycles 5-FU (1000 mg/m(2)/day on days 1-4 and 29-32), along with MMC (10-15 mg/m(2)), given on either day 1 alone (n = 154), or days 1 and 29 (n = 63). Outcomes included progression-free (PFS), cancer-specific (CSS), overall (OS), and colostomy-free survival (CFS), as well as toxicity criteria. RESULTS Median age 60 years, 70% female, 52% T3-T4, and 40% node-positive. Median follow-up 26 months. At 2 years, outcomes were: PFS 80%, CSS 89%, OS 86%, and CFS 88%. There was no difference in PFS (HR 0.85, 95% CI 0.37-1.92), CSS (HR 0.32, 95% CI 0.07-1.42), OS (HR 0.67, 95% CI 0.25-1.83), or CFS (HR 0.91, 95% CI 0.31-2.67) between the MMC1 and MMC2 groups. Stage and male gender were predictive of worse outcomes. Acute grade ⩾ 2 toxicities were worse in the MMC2 group. There were 3 treatment-related deaths, all in the MMC2 group. CONCLUSIONS This study suggests that MMC1 is efficacious and may be an alternative to MMC2 in patients with anal cancer treated with definitive chemoradiation, with the potential for less acute treatment-related toxicity. Randomized trials comparing these two regimens could be considered.

Carcinoma of the tonsillar area treated with external radiotherapy alone

Seventy patients with carcinoma of the tonsillar area were treated with radiation therapy alone, all with a minimum follow-up of 3 years. Seventeen patients with stages I and II developed six recurrences and three were salvaged by surgery. Fifty-three patients with stages III and IV developed 24 recurrences, and only three could be salvaged by surgery. We conclude that radiation therapy is adequate for stages I and II carcinoma of the tonsillar area. Local control rate is satisfactory and surgical salvage is acceptable. Patients with advanced disease, Stages III and IV, have a poor survival rate with radiotherapy alone. Local recurrence is high and surgical salvage is inadequate. We have decided to offer selected patients with stages III and IV tonsillar carcinoma planned combined radiotherapy and surgery, in an effort to improve the survival rate.

Observations on the treatment of mediastinal masses in Hodgkin's disease emphasizing site of failure.

Of 244 patients with Hodgkins disease, 126 (52%) had an abnormal mediastinum. Sixty-four patients were treated with radiation, 36 with radiation and chemotherapy, and 25 with chemotherapy alone as an initial treatment. Twenty of 52 (38%) with stage I or II who received initially radiation alone relapsed, and 70% (14 of 20) of them were salvaged with chemotherapy. Therefore, the ultimate failure rate was 12% (6 of 52). Forty percent (8 of 20) of these patients failed within or at the margin of the radiation portal, and 60% failed predominantly outside of the radiation field. Even though we did not treat the whole lung prophylactically, there was only one true peripheral lung recurrence. Nine of 20 (45%) recurred in more than one site. Of 36 patients treated with combined radiation and chemotherapy, 21 patients had stage I, II, or IIIA disease. Of these, two patients relapsed. Of 86 patients with accessible x-ray films, 30 patients had large masses with a ratio of mass to transverse diameter greater than .33 at the broadest level. Fifty-six patients had small masses. Survival at 96 months in patients with stages I-IIIA with either large or small masses is 94% (p = 0.80). Their relapse-free survival at 96 months is 79% for large masses and 95% for small masses (p = 0.18). The site of relapse is discussed in detail in the text. There were five treatment-related deaths; three patients died of acute myelogenous leukemia. Our data do not support the role of whole-lung prophylactic irradiation or initial combined radiotherapy and chemotherapy in patients with large mediastinal masses.

Systemic absorption of conjugated estrogenic cream by the irradiated vagina.

Abstract Previous authors have documented systemic absorption of vaginal estrogenic creams (VEC) in nonirradiated postmenopausal women. Our present study demonstrates that postmenopausal women who have received pelvic irradiation for carcinoma of the uterine cervix absorb a conjugated equine estrogenic vaginal cream (Premarin) comparably to nonirradiated controls. Postabsorptive plasma elevations of estrone and estradiol are sufficient to cause depression of plasma luteinized hormone. Therefore, if systemic estrogen is contraindicated for other medical reasons in postirradiated patients, vaginal cream does not provide safety. On the other hand, if estrogen therapy is deemed necessary, physiological (luteal phase) plasma estrogen levels will develop with either vaginal or oral use. Convenience and patient acceptance might suggest prescribing oral preparations for postirradiation vaginitis. Metabolic conversion products differ according to route of administration. Since controversy prevails as to which estrogen metabolites carry less risk of neoplasia in liver, breast, and endometrium, no preferred type of estrogen preparation nor route of administration can be specified at this time.